[{"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","title":"Cortical development dynamics across autism spectrum disorder mouse models","has_accepted_license":"1","OA_type":"hybrid","OA_place":"publisher","status":"public","day":"17","related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/patterns-in-genetic-chaos/","description":"News on ISTA website"}]},"month":"06","corr_author":"1","department":[{"_id":"AnKi"},{"_id":"GaNo"},{"_id":"TiVo"},{"_id":"ScienComp"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"PreCl"}],"project":[{"name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders","grant_number":"101044865","_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6"},{"name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","grant_number":"707964","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Neurobiology of anxiety in autism spectrum disorders","_id":"ebb38b5d-77a9-11ec-83b8-a42e08120a88","grant_number":"FG1803 49015"}],"PlanS_conform":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Despite the functional diversity of over 100 causal genes1,2,3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD."}],"_id":"22295","external_id":{"pmid":["42310454"]},"dataavailabilitystatement":"Single-nucleus multiomics data are available from the Gene Expression Omnibus (GSE328363). The mm10 reference genome was used for the alignment (refdata-cellranger-arc-mm10-2020-A-2.0.0, obtained from https://cf.10xgenomics.com/supp/cell-arc/refdata-cellranger-arc-mm10-2020-A-2.0.0.tar.gz). Single-cell data can be accessed and visualized through a CELLxGENE database (https://adameykolab.hifo.meduniwien.ac.at/cellxgene_public/filecrawl/.2026_Nature_Schwarz). Source data are provided with this paper. Scripts and analyses that support the main findings of this study are accessible in a GitHub repository (https://git.ista.ac.at/research-sofware/mouseome).","date_updated":"2026-08-04T09:29:55Z","quality_controlled":"1","pmid":1,"publication":"Nature","date_published":"2026-06-17T00:00:00Z","doi":"10.1038/s41586-026-10679-1","fulldoi":"https://doi.org/10.1038/s41586-026-10679-1","scopus_import":"1","article_processing_charge":"Yes (via OA deal)","year":"2026","date_created":"2026-07-13T09:47:21Z","publication_status":"epub_ahead","article_type":"original","type":"journal_article","main_file_link":[{"url":"https://doi.org/10.1038/s41586-026-10679-1","open_access":"1"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"citation":{"ieee":"L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026.","ama":"Schwarz LA, Dotter C, Isaev S, et al. Cortical development dynamics across autism spectrum disorder mouse models. <i>Nature</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41586-026-10679-1\">10.1038/s41586-026-10679-1</a>","short":"L.A. Schwarz, C. Dotter, S. Isaev, M. Lisi, D. Malzl, C. Büschl, S. Ladstätter, B. Oliveira, M. Barel, B. Basilico, C. Chintaluri, S. Gorkiewicz, M. Goudarzi, T. Belinova, S. Reichl, G. Sendžikaitė, S. Arcot Jayaram, P. Koppensteiner, C.M. Sommer, T.P. Vogels, J. Menche, I. Adameyko, P.V. Kharchenko, C. Bock, G. Novarino, Nature (2026).","apa":"Schwarz, L. A., Dotter, C., Isaev, S., Lisi, M., Malzl, D., Büschl, C., … Novarino, G. (2026). Cortical development dynamics across autism spectrum disorder mouse models. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-026-10679-1\">https://doi.org/10.1038/s41586-026-10679-1</a>","ista":"Schwarz LA, Dotter C, Isaev S, Lisi M, Malzl D, Büschl C, Ladstätter S, Oliveira B, Barel M, Basilico B, Chintaluri C, Gorkiewicz S, Goudarzi M, Belinova T, Reichl S, Sendžikaitė G, Arcot Jayaram S, Koppensteiner P, Sommer CM, Vogels TP, Menche J, Adameyko I, Kharchenko PV, Bock C, Novarino G. 2026. Cortical development dynamics across autism spectrum disorder mouse models. Nature.","mla":"Schwarz, Lena A., et al. “Cortical Development Dynamics across Autism Spectrum Disorder Mouse Models.” <i>Nature</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41586-026-10679-1\">10.1038/s41586-026-10679-1</a>.","chicago":"Schwarz, Lena A, Christoph Dotter, Sergey Isaev, Michela Lisi, Daniel Malzl, Christoph Büschl, Sabrina Ladstätter, et al. “Cortical Development Dynamics across Autism Spectrum Disorder Mouse Models.” <i>Nature</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41586-026-10679-1\">https://doi.org/10.1038/s41586-026-10679-1</a>."},"author":[{"id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A","first_name":"Lena A","last_name":"Schwarz"},{"first_name":"Christoph","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter"},{"full_name":"Isaev, Sergey","first_name":"Sergey","last_name":"Isaev"},{"full_name":"Lisi, Michela","id":"39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c","first_name":"Michela","last_name":"Lisi"},{"last_name":"Malzl","full_name":"Malzl, Daniel","first_name":"Daniel"},{"full_name":"Büschl, Christoph","id":"2a8c054c-0913-11ee-9159-f8ef515809ed","first_name":"Christoph","last_name":"Büschl"},{"full_name":"Ladstätter, Sabrina","first_name":"Sabrina","last_name":"Ladstätter"},{"last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","first_name":"Bárbara"},{"id":"8959927b-2236-11ed-bd6e-ea83d94ade0e","full_name":"Barel, Matteo","first_name":"Matteo","last_name":"Barel"},{"last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Chintaluri","first_name":"Chaitanya","id":"BA06AFEE-A4BA-11EA-AE5C-14673DDC885E","orcid":"0000-0003-4252-1608","full_name":"Chintaluri, Chaitanya"},{"first_name":"Sarah","full_name":"Gorkiewicz, Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","last_name":"Gorkiewicz"},{"first_name":"Mohammad","id":"3384113A-F248-11E8-B48F-1D18A9856A87","full_name":"Goudarzi, Mohammad","last_name":"Goudarzi"},{"first_name":"Tereza","full_name":"Belinova, Tereza","id":"0bf89b6a-d28b-11eb-8bd6-f43768e4d368","last_name":"Belinova"},{"full_name":"Reichl, Stephan","first_name":"Stephan","last_name":"Reichl"},{"first_name":"Gintarė","full_name":"Sendžikaitė, Gintarė","id":"dd6d52f2-c50d-11eb-9548-bcf0ff82b344","last_name":"Sendžikaitė"},{"last_name":"Arcot Jayaram","first_name":"Satish","id":"b0bbee33-09f7-11eb-909c-8b358058d28a","full_name":"Arcot Jayaram, Satish","orcid":"0000-0002-2479-2669"},{"full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter","last_name":"Koppensteiner"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer"},{"last_name":"Vogels","first_name":"Tim P","orcid":"0000-0003-3295-6181","full_name":"Vogels, Tim P","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425"},{"last_name":"Menche","full_name":"Menche, Jörg","first_name":"Jörg"},{"last_name":"Adameyko","first_name":"Igor","full_name":"Adameyko, Igor"},{"last_name":"Kharchenko","full_name":"Kharchenko, Peter Vasili","id":"0095641e-7eb7-11f1-8665-aec51a2ab5e0","first_name":"Peter Vasili"},{"last_name":"Bock","first_name":"Christoph","full_name":"Bock, Christoph"},{"last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"license":"https://creativecommons.org/licenses/by/4.0/","supplementarymaterial":"yes","publisher":"Springer Nature","researchdata_availability":"yes","ddc":["570"],"oa":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"acknowledgement":"We thank F. Freeman, V. Voronin and M. Ladron de Guevara for technical assistance; A. Stichelberger and S. Liegenfeld for the management of our animal colony; M. Schunn, C. Gold and the Preclinical Facility team for technical assistance; C. Jansen and the Scientific Computing Facility for bioinformatics support and technical assistance; the Biomedical Sequencing Facility at CeMM for assistance with next-generation sequencing; and J. Lin and T. Krausgruber in the laboratory of C. Bock for support with flow cytometry; J. Kirchner for illustrating the multi-omics approach depicted in Fig. 1; and all members of the laboratory of G.N. for their support and discussions. This study was supported by the Scientific Service Units of ISTA through resources provided by the Imaging & Optics Facility and the Laboratory Support Facility. Bulk RNA-seq was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities, member of the Vienna BioCenter. This work was supported by a European Research Council Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02) and by the Austrian Science Fund (PE1028W1232 and PR1028FG1803) to G.N. Open access funding provided by Institute of Science and Technology (IST Austria)."},{"date_updated":"2026-09-16T07:33:54Z","quality_controlled":"1","intvolume":"        45","date_published":"2026-04-28T00:00:00Z","publication":"Cell Reports","pmid":1,"scopus_import":"1","article_processing_charge":"Yes","fulldoi":"https://doi.org/10.1016/j.celrep.2026.117227","doi":"10.1016/j.celrep.2026.117227","publication_status":"published","date_created":"2026-04-19T22:07:43Z","article_type":"original","year":"2026","has_accepted_license":"1","OA_place":"publisher","OA_type":"gold","title":"Multifold increase in spinal inhibitory cell types with emergence of limb movement","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","related_material":{"record":[{"relation":"dissertation_contains","id":"22667","status":"public"}]},"day":"28","month":"04","status":"public","abstract":[{"lang":"eng","text":"As vertebrates transitioned from water to land, locomotion shifted from undulatory swimming to limb-based movement. How spinal circuits and their cell types evolved to support this transition remains unclear. We leverage frog metamorphosis, which recapitulates this transition within a single organism, to define how spinal circuits generate aquatic versus terrestrial motor patterns. At swim stages, spinal architecture is uniform, with a transcriptionally and anatomically homogeneous motor and interneurons. As limbs develop and their movement complexifies, spinal circuits expand in neuron number and subtype diversity. This expansion is most pronounced for V1 inhibitory neurons, which increase ∼70-fold and diversify into transcriptionally distinct subtypes. Disrupting transcription factors defining emerging motor and V1 populations reveals molecular segregation between swim and limb circuits, highlighting the role of subtype diversity in motor coordination. A multifold increase in inhibitory neuron diversity thus underlies the tail-to-limb locomotor transition, providing a framework for spinal circuit adaptation during vertebrate evolution."}],"_id":"21746","PlanS_conform":"1","oa_version":"Published Version","project":[{"_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","grant_number":"101041551","name":"Development and Evolution of Tetrapod Motor Circuits"},{"grant_number":"F7814","_id":"8da85f50-16d5-11f0-9cad-eab8b0ff6c9e","name":"Stem Cell Modulation in Neural Development and Regeneration/ P14-Swim-to-limb transition: cell type to connection diversity"},{"_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","grant_number":"CZI01","name":"Tools for automation and feedback microscopy"},{"name":"Development of V1 interneuron diversity during swim-to-walk transition of Xenopus metamorphosis","_id":"bd73af52-d553-11ed-ba76-912049f0ac7a","grant_number":"FTI21-D-046"},{"grant_number":"COE16","_id":"cf428362-b037-11f1-b015-8277a8a2f63d","name":"Neuronal circuits in health and disease (Sweeney)"}],"department":[{"_id":"LoSw"},{"_id":"GradSch"},{"_id":"TiVo"},{"_id":"Bio"},{"_id":"NiBa"}],"external_id":{"pmid":["41964955 "]},"ddc":["570"],"publisher":"Elsevier","language":[{"iso":"eng"}],"oa":1,"volume":45,"publication_identifier":{"issn":["2639-1856"],"eissn":["2211-1247"]},"file":[{"content_type":"application/pdf","date_created":"2026-05-04T12:20:10Z","access_level":"open_access","relation":"main_file","checksum":"0d26cdb5b8d8dec3a911d8261a65cdef","success":1,"creator":"dernst","file_id":"21795","date_updated":"2026-05-04T12:20:10Z","file_name":"2026_CellReports_Vijatovic.pdf","file_size":14925958}],"acknowledgement":"We would like to thank the members of the Sweeney Lab, Mario de Bono, Michael Forsthofer, Katharina Lust, and Meital Oren, for comments on the manuscript. We are also grateful to Tom Jessell and Chris Kintner for their scientific insight and mentorship during the conception of this project. It would also have not been possible without the technical support of the Aquatics and Imaging and Optics Facility support teams (ISTA). We thank Martin Estermann for preparing the initial draft of the graphical abstract and Niki Barolini for the final version. In addition, we thank our funding sources for providing the resources to do these experiments: GFF NÖ FTI Strategy Lower Austria dissertation grant FT121-D-046 (to D.V.), Horizon Europe ERC starting grant 101041551 (to Y.I., L.B.S., F.A.T., and D.V.), Special Research Program (SFB) of the Austrian Science Fund (FWF) project F7814-B (to L.B.S.), Austrian Science Fund (FWF) 10.55776/COE16 (to Y.I. and L.B.S.), NINDS 5R35NS116858 (to J.S.D.), CZI grant DAF2020-225401 (DOI) 10.37921/120055ratwvi (to R.H.), NIH grant R01NS123116 (to J.B.B.), American Lebanese Syrian Associated Charities (ALSAC) (to J.B.B.), German Academic Exchange Service (DAAD) IFI grant 57515251-91853472 (to Z.H.), and Project A.L.S. (to S.B.-M.).","article_number":"117227","issue":"4","type":"journal_article","author":[{"orcid":"0000-0002-5494-0941","full_name":"Vijatovic, David","id":"cf391e77-ec3c-11ea-a124-d69323410b58","first_name":"David","last_name":"Vijatovic"},{"full_name":"Toma, Florina Alexandra ","id":"2f73f876-f128-11eb-9611-b96b5a30cb0e","first_name":"Florina Alexandra ","last_name":"Toma"},{"first_name":"Y","full_name":"Ignatyev, Y","last_name":"Ignatyev"},{"id":"a8144562-32c9-11ee-b5ce-d9800628bda2","full_name":"Harrington, Zoe P","orcid":"0009-0008-0158-4032","first_name":"Zoe P","last_name":"Harrington"},{"last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","first_name":"Robert"},{"last_name":"Smits","full_name":"Smits, Matthijs Geert","id":"7a231d52-e216-11ee-a0bb-8acd55f8f1f0","first_name":"Matthijs Geert"},{"last_name":"Dalla Vecchia","first_name":"Marco","id":"02a7a869-ff06-11ed-a87f-86649d6077e5","full_name":"Dalla Vecchia, Marco"},{"last_name":"Trevisan","full_name":"Trevisan, Alexandra J.","first_name":"Alexandra J."},{"last_name":"Chapman","first_name":"Phillip","full_name":"Chapman, Phillip"},{"last_name":"Julseth","first_name":"Mara","id":"1cf464b2-dc7d-11ea-9b2f-f9b1aa9417d1","full_name":"Julseth, Mara"},{"last_name":"Brenner-Morton","full_name":"Brenner-Morton, Susan","first_name":"Susan"},{"last_name":"Gabitto","first_name":"Mariano I.","full_name":"Gabitto, Mariano I."},{"last_name":"Dasen","first_name":"Jeremy S.","full_name":"Dasen, Jeremy S."},{"last_name":"Bikoff","full_name":"Bikoff, Jay B.","first_name":"Jay B."},{"last_name":"Sweeney","first_name":"Lora Beatrice Jaeger","full_name":"Sweeney, Lora Beatrice Jaeger","orcid":"0000-0001-9242-5601","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425"}],"file_date_updated":"2026-05-04T12:20:10Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"citation":{"short":"D. Vijatovic, F.A. Toma, Y. Ignatyev, Z.P. Harrington, C.M. Sommer, R. Hauschild, M.G. Smits, M. Dalla Vecchia, A.J. Trevisan, P. Chapman, M. Julseth, S. Brenner-Morton, M.I. Gabitto, J.S. Dasen, J.B. Bikoff, L.B. Sweeney, Cell Reports 45 (2026).","ieee":"D. Vijatovic <i>et al.</i>, “Multifold increase in spinal inhibitory cell types with emergence of limb movement,” <i>Cell Reports</i>, vol. 45, no. 4. Elsevier, 2026.","ama":"Vijatovic D, Toma FA, Ignatyev Y, et al. Multifold increase in spinal inhibitory cell types with emergence of limb movement. <i>Cell Reports</i>. 2026;45(4). doi:<a href=\"https://doi.org/10.1016/j.celrep.2026.117227\">10.1016/j.celrep.2026.117227</a>","chicago":"Vijatovic, David, Florina Alexandra  Toma, Y Ignatyev, Zoe P Harrington, Christoph M Sommer, Robert Hauschild, Matthijs Geert Smits, et al. “Multifold Increase in Spinal Inhibitory Cell Types with Emergence of Limb Movement.” <i>Cell Reports</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.celrep.2026.117227\">https://doi.org/10.1016/j.celrep.2026.117227</a>.","apa":"Vijatovic, D., Toma, F. A., Ignatyev, Y., Harrington, Z. P., Sommer, C. M., Hauschild, R., … Sweeney, L. B. (2026). Multifold increase in spinal inhibitory cell types with emergence of limb movement. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2026.117227\">https://doi.org/10.1016/j.celrep.2026.117227</a>","ista":"Vijatovic D, Toma FA, Ignatyev Y, Harrington ZP, Sommer CM, Hauschild R, Smits MG, Dalla Vecchia M, Trevisan AJ, Chapman P, Julseth M, Brenner-Morton S, Gabitto MI, Dasen JS, Bikoff JB, Sweeney LB. 2026. Multifold increase in spinal inhibitory cell types with emergence of limb movement. Cell Reports. 45(4), 117227.","mla":"Vijatovic, David, et al. “Multifold Increase in Spinal Inhibitory Cell Types with Emergence of Limb Movement.” <i>Cell Reports</i>, vol. 45, no. 4, 117227, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.celrep.2026.117227\">10.1016/j.celrep.2026.117227</a>."},"DOAJ_listed":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}]},{"article_number":"koaf006","issue":"4","type":"journal_article","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"},{"_id":"M-Shop"}],"file_date_updated":"2025-07-31T07:03:43Z","author":[{"last_name":"Gallei","first_name":"Michelle C","full_name":"Gallei, Michelle C","orcid":"0000-0003-1286-7368","id":"35A03822-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Truckenbrodt","first_name":"Sven M","id":"45812BD4-F248-11E8-B48F-1D18A9856A87","full_name":"Truckenbrodt, Sven M"},{"first_name":"Caroline","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger"},{"last_name":"Inumella","first_name":"Syamala","id":"F8660870-D756-11E9-98C5-34DFE5697425","orcid":"0009-0002-5890-120X","full_name":"Inumella, Syamala"},{"last_name":"Vistunou","full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","first_name":"Vitali"},{"first_name":"Christoph M","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer"},{"first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854","last_name":"Tavakoli"},{"id":"40E7F008-F248-11E8-B48F-1D18A9856A87","full_name":"Agudelo Duenas, Nathalie","first_name":"Nathalie","last_name":"Agudelo Duenas"},{"last_name":"Vorlaufer","full_name":"Vorlaufer, Jakob","orcid":"0009-0000-7590-3501","id":"937696FA-C996-11E9-8C7C-CF13E6697425","first_name":"Jakob"},{"last_name":"Jahr","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0201-2315","full_name":"Jahr, Wiebke","first_name":"Wiebke"},{"last_name":"Randuch","first_name":"Marek","full_name":"Randuch, Marek","id":"6ac4636d-15b2-11ec-abd3-fb8df79972ae"},{"last_name":"Johnson","first_name":"Alexander J","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","full_name":"Johnson, Alexander J","orcid":"0000-0002-2739-8843"},{"id":"38F4F166-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8510-9739","full_name":"Benková, Eva","first_name":"Eva","last_name":"Benková"},{"first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","last_name":"Friml"},{"last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"citation":{"short":"M.C. Gallei, S.M. Truckenbrodt, C. Kreuzinger, S. Inumella, V. Vistunou, C.M. Sommer, M. Tavakoli, N. Agudelo Duenas, J. Vorlaufer, W. Jahr, M. Randuch, A.J. Johnson, E. Benková, J. Friml, J.G. Danzl, The Plant Cell 37 (2025).","ama":"Gallei MC, Truckenbrodt SM, Kreuzinger C, et al. Super-resolution expansion microscopy in plant roots. <i>The Plant Cell</i>. 2025;37(4). doi:<a href=\"https://doi.org/10.1093/plcell/koaf006\">10.1093/plcell/koaf006</a>","ieee":"M. C. Gallei <i>et al.</i>, “Super-resolution expansion microscopy in plant roots,” <i>The Plant Cell</i>, vol. 37, no. 4. Oxford University Press, 2025.","chicago":"Gallei, Michelle C, Sven M Truckenbrodt, Caroline Kreuzinger, Syamala Inumella, Vitali Vistunou, Christoph M Sommer, Mojtaba Tavakoli, et al. “Super-Resolution Expansion Microscopy in Plant Roots.” <i>The Plant Cell</i>. Oxford University Press, 2025. <a href=\"https://doi.org/10.1093/plcell/koaf006\">https://doi.org/10.1093/plcell/koaf006</a>.","mla":"Gallei, Michelle C., et al. “Super-Resolution Expansion Microscopy in Plant Roots.” <i>The Plant Cell</i>, vol. 37, no. 4, koaf006, Oxford University Press, 2025, doi:<a href=\"https://doi.org/10.1093/plcell/koaf006\">10.1093/plcell/koaf006</a>.","ista":"Gallei MC, Truckenbrodt SM, Kreuzinger C, Inumella S, Vistunou V, Sommer CM, Tavakoli M, Agudelo Duenas N, Vorlaufer J, Jahr W, Randuch M, Johnson AJ, Benková E, Friml J, Danzl JG. 2025. Super-resolution expansion microscopy in plant roots. The Plant Cell. 37(4), koaf006.","apa":"Gallei, M. C., Truckenbrodt, S. M., Kreuzinger, C., Inumella, S., Vistunou, V., Sommer, C. M., … Danzl, J. G. (2025). Super-resolution expansion microscopy in plant roots. <i>The Plant Cell</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/plcell/koaf006\">https://doi.org/10.1093/plcell/koaf006</a>"},"language":[{"iso":"eng"}],"oa":1,"ddc":["580"],"publisher":"Oxford University Press","file":[{"file_id":"20092","creator":"dernst","success":1,"file_size":53904111,"date_updated":"2025-07-31T07:03:43Z","file_name":"2025_PlantCell_Gallei.pdf","access_level":"open_access","content_type":"application/pdf","date_created":"2025-07-31T07:03:43Z","checksum":"9d3f8218ff37a29f29c48a7bbe831bd3","relation":"main_file"}],"acknowledgement":"We gratefully acknowledge support by the Scientific Service Units at ISTA, including the Imaging and Optics and Lab Support facilities and the mechanical workshop and Library. We thank Philipp Velicky for STED microscope alignment.\r\nThis project has received funding from the European Research Council under the Horizon 2020 Framework Programme (grant agreement No 742985, J.F.). It has also received funding from the Horizon 2020 Framework Programme under the Marie Skłodowska-Curie Grant Agreement No. 665385 (M.G.). S.T. has received funding as an ISTplus Fellow from the Horizon 2020 Framework Programme under Marie Skłodowska-Curie grant agreement no. 754411 and from EMBO via a Long-Term Fellowship (grant number ALTF 679-2018). M.R.T. received funding from the Austrian Academy of Sciences with DOC fellowship no. 26137. The project has further received funding from the Austrian Science Fund, via grant DK W1232 (M.R.T., N.A.D., and J.G.D). W.J. received a postdoctoral fellowship from the Human Frontier Science Program (LT000557/2018). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","volume":37,"publication_identifier":{"issn":["1040-4651"],"eissn":["1532-298X"]},"corr_author":"1","status":"public","isi":1,"day":"01","related_material":{"record":[{"id":"18837","relation":"research_data","status":"public"},{"id":"18689","relation":"earlier_version","status":"public"}]},"month":"04","OA_type":"hybrid","has_accepted_license":"1","OA_place":"publisher","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Super-resolution expansion microscopy in plant roots","external_id":{"isi":["001462763100001"],"pmid":["39792900"]},"oa_version":"Published Version","PlanS_conform":"1","_id":"19003","ec_funded":1,"abstract":[{"text":"Super-resolution methods provide far better spatial resolution than the optical diffraction limit of about half the wavelength of light (∼200-300 nm). Nevertheless, they have yet to attain widespread use in plants, largely due to plants’ challenging optical properties. Expansion microscopy improves effective resolution by isotropically increasing the physical distances between sample structures while preserving relative spatial arrangements and clearing the sample. However, its application to plants has been hindered by the rigid, mechanically cohesive structure of plant tissues. Here, we report on whole-mount expansion microscopy of thale cress (Arabidopsis thaliana) root tissues (PlantEx), achieving a four-fold resolution increase over conventional microscopy. Our results highlight the microtubule cytoskeleton organization and interaction between molecularly defined cellular constituents. Combining PlantEx with stimulated emission depletion (STED) microscopy, we increase nanoscale resolution and visualize the complex organization of subcellular organelles from intact tissues by example of the densely packed COPI-coated vesicles associated with the Golgi apparatus and put these into a cellular structural context. Our results show that expansion microscopy can be applied to increase effective imaging resolution in Arabidopsis root specimens. ","lang":"eng"}],"project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020","_id":"261099A6-B435-11E9-9278-68D0E5697425","grant_number":"742985"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"},{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"grant_number":"ALTF 679-2018","_id":"269B5B22-B435-11E9-9278-68D0E5697425","name":"UltraX - achieving sub-nanometer resolution in light microscopy using iterative X10 microscopy in combination with nanobodies and STED"},{"grant_number":"26137","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy"},{"_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF"}],"department":[{"_id":"EvBe"},{"_id":"JoDa"},{"_id":"JiFr"}],"date_published":"2025-04-01T00:00:00Z","pmid":1,"publication":"The Plant Cell","quality_controlled":"1","date_updated":"2026-10-01T11:19:12Z","intvolume":"        37","publication_status":"published","article_type":"original","date_created":"2025-02-05T06:52:06Z","year":"2025","article_processing_charge":"Yes (via OA deal)","scopus_import":"1","doi":"10.1093/plcell/koaf006","fulldoi":"https://doi.org/10.1093/plcell/koaf006"},{"has_accepted_license":"1","OA_place":"publisher","OA_type":"hybrid","title":"Light-microscopy-based connectomic reconstruction of mammalian brain tissue","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","corr_author":"1","related_material":{"record":[{"id":"18697","relation":"research_data","status":"public"},{"relation":"earlier_version","id":"18677","status":"public"}],"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/piecing-together-the-brain-puzzle/","description":"News on ISTA website"}]},"month":"06","day":"12","isi":1,"status":"public","abstract":[{"text":"The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular labelling. Light microscopy is uniquely positioned to visualize specific molecules, but dense, synapse-level circuit reconstruction by light microscopy has been out of reach, owing to limitations in resolution, contrast and volumetric imaging capability. Here we describe light-microscopy-based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning-based segmentation and analysis of connectivity, thereby directly incorporating molecular information into synapse-level reconstructions of brain tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological experiments in a readily adoptable manner.","lang":"eng"}],"_id":"19704","ec_funded":1,"oa_version":"Published Version","PlanS_conform":"1","project":[{"name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","grant_number":"26137"},{"name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"grant_number":"101044865","_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"department":[{"_id":"JoDa"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"GaNo"}],"external_id":{"pmid":["40335689"],"isi":["001483477000001"]},"date_updated":"2026-10-02T09:59:44Z","quality_controlled":"1","intvolume":"       642","date_published":"2025-06-12T00:00:00Z","publication":"Nature","pmid":1,"scopus_import":"1","article_processing_charge":"Yes (via OA deal)","fulldoi":"https://doi.org/10.1038/s41586-025-08985-1","doi":"10.1038/s41586-025-08985-1","date_created":"2025-05-18T22:02:51Z","publication_status":"published","article_type":"original","year":"2025","type":"journal_article","author":[{"last_name":"Tavakoli","full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba"},{"last_name":"Lyudchik","first_name":"Julia","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Michał","full_name":"Januszewski, Michał","last_name":"Januszewski"},{"first_name":"Vitali","full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","last_name":"Vistunou"},{"last_name":"Agudelo Duenas","full_name":"Agudelo Duenas, Nathalie","id":"40E7F008-F248-11E8-B48F-1D18A9856A87","first_name":"Nathalie"},{"last_name":"Vorlaufer","first_name":"Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425","full_name":"Vorlaufer, Jakob","orcid":"0009-0000-7590-3501"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","first_name":"Caroline","last_name":"Kreuzinger"},{"last_name":"Oliveira","first_name":"Bárbara","full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","first_name":"Alban","last_name":"Cenameri"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino"},{"full_name":"Jain, Viren","first_name":"Viren","last_name":"Jain"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl"}],"file_date_updated":"2025-07-03T06:55:20Z","citation":{"ama":"Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy-based connectomic reconstruction of mammalian brain tissue. <i>Nature</i>. 2025;642:398-410. doi:<a href=\"https://doi.org/10.1038/s41586-025-08985-1\">10.1038/s41586-025-08985-1</a>","ieee":"M. Tavakoli <i>et al.</i>, “Light-microscopy-based connectomic reconstruction of mammalian brain tissue,” <i>Nature</i>, vol. 642. Springer Nature, pp. 398–410, 2025.","short":"M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas, J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino, V. Jain, J.G. Danzl, Nature 642 (2025) 398–410.","ista":"Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl JG. 2025. Light-microscopy-based connectomic reconstruction of mammalian brain tissue. Nature. 642, 398–410.","mla":"Tavakoli, Mojtaba, et al. “Light-Microscopy-Based Connectomic Reconstruction of Mammalian Brain Tissue.” <i>Nature</i>, vol. 642, Springer Nature, 2025, pp. 398–410, doi:<a href=\"https://doi.org/10.1038/s41586-025-08985-1\">10.1038/s41586-025-08985-1</a>.","apa":"Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas, N., Vorlaufer, J., … Danzl, J. G. (2025). Light-microscopy-based connectomic reconstruction of mammalian brain tissue. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-025-08985-1\">https://doi.org/10.1038/s41586-025-08985-1</a>","chicago":"Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou, Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy-Based Connectomic Reconstruction of Mammalian Brain Tissue.” <i>Nature</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41586-025-08985-1\">https://doi.org/10.1038/s41586-025-08985-1</a>."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"ddc":["570"],"publisher":"Springer Nature","page":"398-410","language":[{"iso":"eng"}],"oa":1,"volume":642,"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"file":[{"success":1,"creator":"dernst","file_id":"19959","file_name":"2025_Nature_Tavakoli.pdf","date_updated":"2025-07-03T06:55:20Z","file_size":133201290,"access_level":"open_access","date_created":"2025-07-03T06:55:20Z","content_type":"application/pdf","relation":"main_file","checksum":"ebc99d7108e728f46db0a009292675ef"}],"acknowledgement":"We thank S. Dorkenwald and P. Li for critical reading of the manuscript, S. Loomba for discussions and E. Miguel for support with data handling. We acknowledge support from ISTA’s scientific service units: Imaging and Optics, Lab Support, Scientific Computing, the preclinical facility, the Miba Machine Shop and the library. We acknowledge funding from the following sources: Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and M.R.T.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); the European Union’s Horizon 2020 research and innovation programme and Marie Skłodowska-Curie Actions Fellowship 665385 (J.L.); and the European Union’s Horizon 2020 research and innovation programme and European Research Council (ERC) grant 101044865 ‘SecretAutism’ (G.N.).Open access funding provided by Institute of Science and Technology (IST Austria)."},{"doi":"10.1101/2024.09.20.614050","fulldoi":"https://doi.org/10.1101/2024.09.20.614050","article_processing_charge":"No","year":"2024","acknowledgement":"We would like to thank the members of the Sweeney Lab (especially Stavros Papadopoulos and\r\nSophie Gobeil) for their contributions to this project and, in addition to the lab, Graziana Gatto\r\nand Mario de Bono, for discussion, and support. We are also grateful to Tom Jessell and Chris\r\nKintner for their scientific insight and mentorship during the conception of this project. This\r\nproject would also not have been possible with the technical support of the Matthias Nowak,\r\nVerena Mayer and the Aquatics as well as the Imaging and Optics Facility support teams\r\n(ISTA). In addition, we thank our funding sources for providing the resources to do these\r\nexperiments: FTI Strategy Lower Austria Dissertation Grant Number FT121-D-046 (D.V.);\r\nHorizon Europe ERC Starting Grant Number 101041551 (L.B.S., F.A.T. and D.V); Special\r\nResearch Program (SFB) of the Austrian Science Fund (FWF) Project number F7814-B (L.B.S);\r\nNINDS 5R35NS116858 (J.S.D); CZI grant DAF2020-225401 (DOI): 10.37921/120055ratwvi\r\n(R.H.); NIH grant number R01NS123116 (J.B.B); American Lebanese Syrian Associated\r\nCharities (ALSAC) (J.B.B.); German Academic Exchange Service (DAAD) IFI Grant Number\r\n57515251-91853472 (Z.H.); and Project A.L.S. (S.B-M.). ","date_created":"2025-04-07T08:48:28Z","publication_status":"submitted","date_updated":"2025-05-14T11:40:13Z","language":[{"iso":"eng"}],"oa":1,"publication":"bioRxiv","date_published":"2024-09-27T00:00:00Z","department":[{"_id":"LoSw"},{"_id":"TiVo"},{"_id":"Bio"},{"_id":"NiBa"}],"project":[{"name":"Development of V1 interneuron diversity during swim-to-walk transition of Xenopus metamorphosis","grant_number":"FTI21-D-046","_id":"bd73af52-d553-11ed-ba76-912049f0ac7a"},{"name":"Development and Evolution of Tetrapod Motor Circuits","grant_number":"101041551","_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae"},{"name":"Tools for automation and feedback microscopy","_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","grant_number":"CZI01"}],"citation":{"ieee":"D. Vijatovic <i>et al.</i>, “Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis,” <i>bioRxiv</i>. .","ama":"Vijatovic D, Toma FA, Harrington ZP, et al. Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.09.20.614050\">10.1101/2024.09.20.614050</a>","short":"D. Vijatovic, F.A. Toma, Z.P. Harrington, C.M. Sommer, R. Hauschild, A.J. Trevisan, P. Chapman, M. Julseth, S. Brenner-Morton, M.I. Gabitto, J.S. Dasen, J.B. Bikoff, L.B. Sweeney, BioRxiv (n.d.).","mla":"Vijatovic, David, et al. “Spinal Neuron Diversity Scales Exponentially with Swim-to-Limb Transformation during Frog Metamorphosis.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.09.20.614050\">10.1101/2024.09.20.614050</a>.","ista":"Vijatovic D, Toma FA, Harrington ZP, Sommer CM, Hauschild R, Trevisan AJ, Chapman P, Julseth M, Brenner-Morton S, Gabitto MI, Dasen JS, Bikoff JB, Sweeney LB. Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. bioRxiv, <a href=\"https://doi.org/10.1101/2024.09.20.614050\">10.1101/2024.09.20.614050</a>.","apa":"Vijatovic, D., Toma, F. A., Harrington, Z. P., Sommer, C. M., Hauschild, R., Trevisan, A. J., … Sweeney, L. B. (n.d.). Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.09.20.614050\">https://doi.org/10.1101/2024.09.20.614050</a>","chicago":"Vijatovic, David, Florina Alexandra  Toma, Zoe P Harrington, Christoph M Sommer, Robert Hauschild, Alexandra J. Trevisan, Phillip Chapman, et al. “Spinal Neuron Diversity Scales Exponentially with Swim-to-Limb Transformation during Frog Metamorphosis.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.09.20.614050\">https://doi.org/10.1101/2024.09.20.614050</a>."},"oa_version":"Preprint","author":[{"last_name":"Vijatovic","first_name":"David","full_name":"Vijatovic, David","id":"cf391e77-ec3c-11ea-a124-d69323410b58"},{"last_name":"Toma","first_name":"Florina Alexandra ","id":"2f73f876-f128-11eb-9611-b96b5a30cb0e","full_name":"Toma, Florina Alexandra "},{"last_name":"Harrington","id":"a8144562-32c9-11ee-b5ce-d9800628bda2","orcid":"0009-0008-0158-4032","full_name":"Harrington, Zoe P","first_name":"Zoe P"},{"last_name":"Sommer","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"last_name":"Hauschild","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522"},{"full_name":"Trevisan, Alexandra J.","first_name":"Alexandra J.","last_name":"Trevisan"},{"full_name":"Chapman, Phillip","first_name":"Phillip","last_name":"Chapman"},{"last_name":"Julseth","first_name":"Mara","id":"1cf464b2-dc7d-11ea-9b2f-f9b1aa9417d1","full_name":"Julseth, Mara"},{"last_name":"Brenner-Morton","first_name":"Susan","full_name":"Brenner-Morton, Susan"},{"last_name":"Gabitto","full_name":"Gabitto, Mariano I.","first_name":"Mariano I."},{"last_name":"Dasen","first_name":"Jeremy S.","full_name":"Dasen, Jeremy S."},{"full_name":"Bikoff, Jay B.","first_name":"Jay B.","last_name":"Bikoff"},{"last_name":"Sweeney","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","full_name":"Sweeney, Lora Beatrice Jaeger","orcid":"0000-0001-9242-5601","first_name":"Lora Beatrice Jaeger"}],"_id":"19520","abstract":[{"lang":"eng","text":"Vertebrates exhibit a wide range of motor behaviors, ranging from swimming to complex limb-based movements. Here we take advantage of frog metamorphosis, which captures a swim-to-limb-based movement transformation during the development of a single organism, to explore changes in the underlying spinal circuits. We find that the tadpole spinal cord contains small and largely homogeneous populations of motor neurons (MNs) and V1 interneurons (V1s) at early escape swimming stages. These neuronal populations only modestly increase in number and subtype heterogeneity with the emergence of free swimming. In contrast, during frog metamorphosis and the emergence of limb movement, there is a dramatic expansion of MN and V1 interneuron number and transcriptional heterogeneity, culminating in cohorts of neurons that exhibit striking molecular similarity to mammalian motor circuits. CRISPR/Cas9-mediated gene disruption of the limb MN and V1 determinants FoxP1 and Engrailed-1, respectively, results in severe but selective deficits in tail and limb function. Our work thus demonstrates that neural diversity scales exponentially with increasing behavioral complexity and illustrates striking evolutionary conservation in the molecular organization and function of motor circuits across species."}],"acknowledged_ssus":[{"_id":"Bio"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis","type":"preprint","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2024.09.20.614050"}],"OA_place":"repository","OA_type":"green","status":"public","day":"27","month":"09","corr_author":"1"},{"volume":42,"publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"file":[{"relation":"main_file","checksum":"57d5fafb16f02dcb9f7dddb1bd7e2a71","date_created":"2025-01-09T07:48:01Z","content_type":"application/pdf","access_level":"open_access","date_updated":"2025-01-09T07:48:01Z","file_name":"2024_NatureBiotech_Michalska.pdf","file_size":26065165,"success":1,"file_id":"18784","creator":"dernst"}],"acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","ddc":["570"],"publisher":"Springer Nature","page":"1051-1064","oa":1,"language":[{"iso":"eng"}],"file_date_updated":"2025-01-09T07:48:01Z","author":[{"first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","last_name":"Michalska"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik"},{"first_name":"Philipp","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky"},{"last_name":"Korinkova","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana"},{"orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","last_name":"Watson"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105"},{"last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","first_name":"Nicole"},{"first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"last_name":"Czech","full_name":"Czech, Thomas","first_name":"Thomas"},{"first_name":"Romana","full_name":"Höftberger, Romana","last_name":"Höftberger"},{"last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"},{"last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"},{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"citation":{"chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 42, 1051–1064.","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, vol. 42, Springer Nature, 2024, pp. 1051–64, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2024;42:1051-1064. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>, vol. 42. Springer Nature, pp. 1051–1064, 2024."},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"type":"journal_article","article_processing_charge":"Yes (in subscription journal)","scopus_import":"1","doi":"10.1038/s41587-023-01911-8","fulldoi":"https://doi.org/10.1038/s41587-023-01911-8","date_created":"2023-09-03T22:01:15Z","publication_status":"published","article_type":"original","year":"2024","date_updated":"2026-10-02T11:27:12Z","quality_controlled":"1","intvolume":"        42","date_published":"2024-07-01T00:00:00Z","pmid":1,"publication":"Nature Biotechnology","oa_version":"Published Version","_id":"14257","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"ec_funded":1,"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"grant_number":"LS18-022","_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"},{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635"}],"external_id":{"pmid":["37653226"],"isi":["001065254200001"]},"OA_type":"hybrid","has_accepted_license":"1","OA_place":"publisher","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Imaging brain tissue architecture across millimeter to nanometer scales","corr_author":"1","status":"public","isi":1,"month":"07","day":"01","related_material":{"record":[{"id":"18660","relation":"dissertation_contains","status":"deleted"},{"status":"public","id":"13126","relation":"research_data"},{"status":"public","id":"18674","relation":"dissertation_contains"}],"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}]}},{"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2024.02.21.581330"}],"das_tickbox":"0","type":"preprint","license":"https://creativecommons.org/licenses/by-nc/4.0/","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"author":[{"last_name":"Gallei","orcid":"0000-0003-1286-7368","full_name":"Gallei, Michelle C","id":"35A03822-F248-11E8-B48F-1D18A9856A87","first_name":"Michelle C"},{"first_name":"Sven M","id":"45812BD4-F248-11E8-B48F-1D18A9856A87","full_name":"Truckenbrodt, Sven M","last_name":"Truckenbrodt"},{"last_name":"Kreuzinger","first_name":"Caroline","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Inumella","first_name":"Syamala","id":"F8660870-D756-11E9-98C5-34DFE5697425","full_name":"Inumella, Syamala","orcid":"0009-0002-5890-120X"},{"last_name":"Vistunou","full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","first_name":"Vitali"},{"last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli"},{"last_name":"Agudelo Duenas","id":"40E7F008-F248-11E8-B48F-1D18A9856A87","full_name":"Agudelo Duenas, Nathalie","first_name":"Nathalie"},{"id":"937696FA-C996-11E9-8C7C-CF13E6697425","orcid":"0009-0000-7590-3501","full_name":"Vorlaufer, Jakob","first_name":"Jakob","last_name":"Vorlaufer"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0201-2315","full_name":"Jahr, Wiebke","first_name":"Wiebke","last_name":"Jahr"},{"first_name":"Marek","full_name":"Randuch, Marek","id":"6ac4636d-15b2-11ec-abd3-fb8df79972ae","last_name":"Randuch"},{"last_name":"Johnson","first_name":"Alexander J","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","full_name":"Johnson, Alexander J","orcid":"0000-0002-2739-8843"},{"last_name":"Benková","first_name":"Eva","orcid":"0000-0002-8510-9739","full_name":"Benková, Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Friml","first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","short":"CC BY-NC (4.0)","image":"/images/cc_by_nc.png"},"citation":{"mla":"Gallei, Michelle C., et al. “Super-Resolution Expansion Microscopy in Plant Roots.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.02.21.581330\">10.1101/2024.02.21.581330</a>.","ista":"Gallei MC, Truckenbrodt SM, Kreuzinger C, Inumella S, Vistunou V, Sommer CM, Tavakoli M, Agudelo Duenas N, Vorlaufer J, Jahr W, Randuch M, Johnson AJ, Benková E, Friml J, Danzl JG. Super-resolution expansion microscopy in plant roots. bioRxiv, <a href=\"https://doi.org/10.1101/2024.02.21.581330\">10.1101/2024.02.21.581330</a>.","apa":"Gallei, M. C., Truckenbrodt, S. M., Kreuzinger, C., Inumella, S., Vistunou, V., Sommer, C. M., … Danzl, J. G. (n.d.). Super-resolution expansion microscopy in plant roots. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.02.21.581330\">https://doi.org/10.1101/2024.02.21.581330</a>","chicago":"Gallei, Michelle C, Sven M Truckenbrodt, Caroline Kreuzinger, Syamala Inumella, Vitali Vistunou, Christoph M Sommer, Mojtaba Tavakoli, et al. “Super-Resolution Expansion Microscopy in Plant Roots.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.02.21.581330\">https://doi.org/10.1101/2024.02.21.581330</a>.","ieee":"M. C. Gallei <i>et al.</i>, “Super-resolution expansion microscopy in plant roots,” <i>bioRxiv</i>. .","ama":"Gallei MC, Truckenbrodt SM, Kreuzinger C, et al. Super-resolution expansion microscopy in plant roots. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.02.21.581330\">10.1101/2024.02.21.581330</a>","short":"M.C. Gallei, S.M. Truckenbrodt, C. Kreuzinger, S. Inumella, V. Vistunou, C.M. Sommer, M. Tavakoli, N. Agudelo Duenas, J. Vorlaufer, W. Jahr, M. Randuch, A.J. Johnson, E. Benková, J. Friml, J.G. Danzl, BioRxiv (n.d.)."},"language":[{"iso":"eng"}],"oa":1,"researchdata_availability":"no","supplementarymaterial":"no","acknowledgement":"We gratefully acknowledge support by the Scientific Service Units at ISTA, including the Imaging and Optics and Lab Support facilities and the mechanical workshop and Library. We thank Philipp Velicky for STED microscope alignment.\r\n\r\nThis project has received funding from the Austrian Science Fund (FWF): I 3630-B25 (J.G.D) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 742985, J.F.). It has also received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665385. S.T. has received funding as an ISTplus Fellow from the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie grant agreement no. 754411 and from an EMBO Long-Term Fellowship (grant number ALTF 679-2018). It has further received funding from the Austrian Science Fund (FWF) grant DK W1232 (M.T, N.A-D., J.G.D). W.J. received funding via a Human Frontier Science Program postdoctoral fellowship LT000557/2018.\r\n\r\nThe funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","corr_author":"1","status":"public","related_material":{"record":[{"status":"public","relation":"later_version","id":"19003"},{"relation":"dissertation_contains","id":"18681","status":"public"}]},"day":"21","month":"02","OA_place":"repository","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","title":"Super-resolution expansion microscopy in plant roots","oa_version":"Preprint","_id":"18689","abstract":[{"lang":"eng","text":"Multiplexed fluorescence microscopy imaging is widely used in biomedical applications. However, simultaneous imaging of multiple fluorophores can result in spectral leaks and overlapping, which greatly degrades image quality and subsequent analysis. Existing popular spectral unmixing methods are mainly based on computational intensive linear models and the performance is heavily dependent on the reference spectra, which may greatly preclude its further applications. In this paper, we propose a deep learning-based blindly spectral unmixing method, termed AutoUnmix, to imitate the physical spectral mixing process. A tranfer learning framework is further devised to allow our AutoUnmix adapting to a variety of imaging systems without retraining the network. Our proposed method has demonstrated real-time unmixing capabilities, surpassing existing methods by up to 100-fold in terms of unmixing speed. We further validate the reconstruction performance on both synthetic datasets and biological samples. The unmixing results of AutoUnmix achieve a highest SSIM of 0.99 in both three- and four-color imaging, with nearly up to 20% higher than other popular unmixing methods. Due to the desirable property of data independency and superior blind unmixing performance, we believe AutoUnmix is a powerful tool to study the interaction process of different organelles labeled by multiple fluorophores."}],"ec_funded":1,"project":[{"grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"},{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"},{"name":"UltraX - achieving sub-nanometer resolution in light microscopy using iterative X10 microscopy in combination with nanobodies and STED","_id":"269B5B22-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 679-2018"}],"department":[{"_id":"EvBe"},{"_id":"JoDa"},{"_id":"JiFr"}],"date_published":"2024-02-21T00:00:00Z","publication":"bioRxiv","date_updated":"2026-10-02T11:27:43Z","date_created":"2024-12-19T12:28:00Z","publication_status":"draft","year":"2024","article_processing_charge":"No","doi":"10.1101/2024.02.21.581330","fulldoi":"https://doi.org/10.1101/2024.02.21.581330"},{"acknowledgement":"We thank Sven Dorkenwald and Peter Li for critical reading of the\r\nmanuscript. We acknowledge expert support by ISTA’s scientific service units: Imaging and\r\nOptics, Lab Support, Scientific Computing, Preclinical Facility, Miba Machine Shop, and Library.\r\nWe gratefully acknowledge funding by the following sources:\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, MRT)\r\nAustrian Academy of Sciences DOC fellowship 26137 (MRT)\r\nEU Horizon 2020 program, Marie Skłodowska-Curie Actions Fellowship 665385 (JL)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research\r\nCouncil (ERC) grant 101044865 “SecretAutism.”\r\n","language":[{"iso":"eng"}],"oa":1,"researchdata_availability":"no","supplementarymaterial":"no","acknowledged_ssus":[{"_id":"E-Lib"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"ScienComp"}],"author":[{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854","first_name":"Mojtaba","last_name":"Tavakoli"},{"last_name":"Lyudchik","first_name":"Julia","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Januszewski, Michał","first_name":"Michał","last_name":"Januszewski"},{"full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","first_name":"Vitali","last_name":"Vistunou"},{"last_name":"Agudelo Duenas","full_name":"Agudelo Duenas, Nathalie","id":"40E7F008-F248-11E8-B48F-1D18A9856A87","first_name":"Nathalie"},{"last_name":"Vorlaufer","id":"937696FA-C996-11E9-8C7C-CF13E6697425","full_name":"Vorlaufer, Jakob","orcid":"0009-0000-7590-3501","first_name":"Jakob"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer"},{"last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","first_name":"Caroline"},{"last_name":"Oliveira","first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara"},{"last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino"},{"first_name":"Viren","full_name":"Jain, Viren","last_name":"Jain"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl"}],"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"citation":{"short":"M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas, J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino, V. Jain, J.G. Danzl, BioRxiv (n.d.).","ama":"Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.03.01.582884\">10.1101/2024.03.01.582884</a>","ieee":"M. Tavakoli <i>et al.</i>, “Light-microscopy based dense connectomic reconstruction of mammalian brain tissue,” <i>bioRxiv</i>. .","chicago":"Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou, Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.03.01.582884\">https://doi.org/10.1101/2024.03.01.582884</a>.","apa":"Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas, N., Vorlaufer, J., … Danzl, J. G. (n.d.). Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.03.01.582884\">https://doi.org/10.1101/2024.03.01.582884</a>","ista":"Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl JG. Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. bioRxiv, <a href=\"https://doi.org/10.1101/2024.03.01.582884\">10.1101/2024.03.01.582884</a>.","mla":"Tavakoli, Mojtaba, et al. “Light-Microscopy Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.03.01.582884\">10.1101/2024.03.01.582884</a>."},"main_file_link":[{"url":"https://doi.org/10.1101/2024.03.01.582884","open_access":"1"}],"type":"preprint","das_tickbox":"0","date_created":"2024-12-18T14:48:24Z","publication_status":"draft","year":"2024","article_processing_charge":"No","fulldoi":"https://doi.org/10.1101/2024.03.01.582884","doi":"10.1101/2024.03.01.582884","date_published":"2024-07-08T00:00:00Z","publication":"bioRxiv","date_updated":"2026-10-02T11:27:43Z","abstract":[{"lang":"eng","text":"The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution with dense cellular labeling. Light microscopy is uniquely positioned to visualize specific molecules but dense, synapse-level circuit reconstruction by light microscopy has been out of reach due to limitations in resolution, contrast, and volumetric imaging capability. Here we developed light-microscopy based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning based segmentation and analysis of connectivity, thus directly incorporating molecular information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level brain tissue phenotyping in biological experiments in a readily adoptable manner."}],"_id":"18677","ec_funded":1,"oa_version":"Preprint","project":[{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","grant_number":"26137","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy"},{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders","_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","grant_number":"101044865"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"department":[{"_id":"GaNo"},{"_id":"JoDa"}],"corr_author":"1","related_material":{"record":[{"relation":"later_version","id":"19704","status":"public"},{"status":"public","relation":"dissertation_contains","id":"18674"},{"status":"public","relation":"dissertation_contains","id":"18681"}]},"month":"07","day":"08","status":"public","OA_place":"repository","title":"Light-microscopy based dense connectomic reconstruction of mammalian brain tissue","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345"},{"status":"public","isi":1,"day":"10","month":"04","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish","has_accepted_license":"1","external_id":{"pmid":["36931269"],"isi":["000982111800001"]},"project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573"},{"name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation","grant_number":"ALTF 850-2017","_id":"26520D1E-B435-11E9-9278-68D0E5697425"},{"name":"Coordination of mesendoderm fate specification and internalization during zebrafish gastrulation","grant_number":"LT000429","_id":"266BC5CE-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"CaHe"},{"_id":"Bio"}],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Interstitial fluid (IF) accumulation between embryonic cells is thought to be important for embryo patterning and morphogenesis. Here, we identify a positive mechanical feedback loop between cell migration and IF relocalization and find that it promotes embryonic axis formation during zebrafish gastrulation. We show that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between the yolk cell and deep cell tissue to extend the embryonic axis, compress the overlying deep cell layer, thereby causing IF to flow from the deep cell layer to the boundary between the yolk cell and the deep cell layer, directly ahead of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion formation and migration by opening up the space into which the ppl moves and, thereby, the ability of the ppl to trigger IF relocalization by pushing against the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic feedback loop between cell migration and IF relocalization."}],"_id":"12830","ec_funded":1,"pmid":1,"publication":"Developmental Cell","date_published":"2023-04-10T00:00:00Z","intvolume":"        58","date_updated":"2025-04-23T08:51:34Z","quality_controlled":"1","year":"2023","date_created":"2023-04-16T22:01:07Z","article_type":"original","publication_status":"published","doi":"10.1016/j.devcel.2023.02.016","fulldoi":"https://doi.org/10.1016/j.devcel.2023.02.016","scopus_import":"1","article_processing_charge":"Yes (via OA deal)","issue":"7","type":"journal_article","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"citation":{"chicago":"Huljev, Karla, Shayan Shamipour, Diana C Nunes Pinheiro, Friedrich Preusser, Irene Steccari, Christoph M Sommer, Suyash Naik, and Carl-Philipp J Heisenberg. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” <i>Developmental Cell</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.devcel.2023.02.016\">https://doi.org/10.1016/j.devcel.2023.02.016</a>.","mla":"Huljev, Karla, et al. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” <i>Developmental Cell</i>, vol. 58, no. 7, Elsevier, 2023, p. 582–596.e7, doi:<a href=\"https://doi.org/10.1016/j.devcel.2023.02.016\">10.1016/j.devcel.2023.02.016</a>.","ista":"Huljev K, Shamipour S, Nunes Pinheiro DC, Preusser F, Steccari I, Sommer CM, Naik S, Heisenberg C-PJ. 2023. A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. Developmental Cell. 58(7), 582–596.e7.","apa":"Huljev, K., Shamipour, S., Nunes Pinheiro, D. C., Preusser, F., Steccari, I., Sommer, C. M., … Heisenberg, C.-P. J. (2023). A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2023.02.016\">https://doi.org/10.1016/j.devcel.2023.02.016</a>","short":"K. Huljev, S. Shamipour, D.C. Nunes Pinheiro, F. Preusser, I. Steccari, C.M. Sommer, S. Naik, C.-P.J. Heisenberg, Developmental Cell 58 (2023) 582–596.e7.","ama":"Huljev K, Shamipour S, Nunes Pinheiro DC, et al. A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. <i>Developmental Cell</i>. 2023;58(7):582-596.e7. doi:<a href=\"https://doi.org/10.1016/j.devcel.2023.02.016\">10.1016/j.devcel.2023.02.016</a>","ieee":"K. Huljev <i>et al.</i>, “A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish,” <i>Developmental Cell</i>, vol. 58, no. 7. Elsevier, p. 582–596.e7, 2023."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"file_date_updated":"2023-04-17T07:41:25Z","author":[{"last_name":"Huljev","first_name":"Karla","id":"44C6F6A6-F248-11E8-B48F-1D18A9856A87","full_name":"Huljev, Karla"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","full_name":"Shamipour, Shayan","first_name":"Shayan","last_name":"Shamipour"},{"last_name":"Nunes Pinheiro","first_name":"Diana C","full_name":"Nunes Pinheiro, Diana C","orcid":"0000-0003-4333-7503","id":"2E839F16-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Preusser","first_name":"Friedrich","full_name":"Preusser, Friedrich"},{"last_name":"Steccari","first_name":"Irene","id":"2705C766-9FE2-11EA-B224-C6773DDC885E","full_name":"Steccari, Irene"},{"last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"2C0B105C-F248-11E8-B48F-1D18A9856A87","full_name":"Naik, Suyash","orcid":"0000-0001-8421-5508","first_name":"Suyash","last_name":"Naik"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"language":[{"iso":"eng"}],"page":"582-596.e7","publisher":"Elsevier","ddc":["570"],"acknowledgement":"We thank Andrea Pauli (IMP) and Edouard Hannezo (ISTA) for fruitful discussions and support with the SPIM experiments; the Heisenberg group, and especially Feyza Nur Arslan and Alexandra Schauer, for discussions and feedback; Michaela Jović (ISTA) for help with the quantitative real-time PCR protocol; the bioimaging and zebrafish facilities of ISTA for continuous support; Stephan Preibisch (Janelia Research Campus) for support with the SPIM data analysis; and Nobuhiro Nakamura (Tokyo Institute of Technology) for sharing α1-Na+/K+-ATPase antibody. This work was supported by funding from the European Union (European Research Council Advanced grant 742573 to C.-P.H.), postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P., and a PhD fellowship from the Studienstiftung des deutschen Volkes to F.P.","file":[{"relation":"main_file","checksum":"c80ca2ebc241232aacdb5aa4b4c80957","date_created":"2023-04-17T07:41:25Z","access_level":"open_access","content_type":"application/pdf","date_updated":"2023-04-17T07:41:25Z","file_name":"2023_DevelopmentalCell_Huljev.pdf","file_size":7925886,"success":1,"creator":"dernst","file_id":"12842"}],"publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"volume":58},{"OA_place":"publisher","has_accepted_license":"1","OA_type":"hybrid","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Dense 4D nanoscale reconstruction of living brain tissue","corr_author":"1","status":"public","isi":1,"related_material":{"record":[{"status":"public","relation":"research_data","id":"12817"},{"status":"public","relation":"shorter_version","id":"14770"},{"relation":"earlier_version","id":"11943","status":"public"},{"status":"public","id":"18674","relation":"dissertation_contains"}],"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}]},"month":"08","day":"01","oa_version":"Published Version","_id":"13267","ec_funded":1,"abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}],"project":[{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232","name":"Molecular Drug Targets","call_identifier":"FWF"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","grant_number":"LS18-022","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"},{"_id":"24F9549A-B435-11E9-9278-68D0E5697425","grant_number":"715767","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","call_identifier":"H2020"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","grant_number":"LT00057","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"date_updated":"2026-10-02T11:27:12Z","quality_controlled":"1","intvolume":"        20","date_published":"2023-08-01T00:00:00Z","pmid":1,"publication":"Nature Methods","article_processing_charge":"Yes (in subscription journal)","scopus_import":"1","doi":"10.1038/s41592-023-01936-6","fulldoi":"https://doi.org/10.1038/s41592-023-01936-6","publication_status":"published","date_created":"2023-07-23T22:01:13Z","article_type":"original","year":"2023","type":"journal_article","file_date_updated":"2025-02-26T08:01:57Z","author":[{"first_name":"Philipp","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky"},{"last_name":"Miguel Villalba","first_name":"Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder","orcid":"0000-0001-5665-0430"},{"last_name":"Michalska","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"last_name":"Wei","full_name":"Wei, Donglai","first_name":"Donglai"},{"full_name":"Lin, Zudi","first_name":"Zudi","last_name":"Lin"},{"last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","first_name":"Jake"},{"full_name":"Troidl, Jakob","first_name":"Jakob","last_name":"Troidl"},{"first_name":"Johanna","full_name":"Beyer, Johanna","last_name":"Beyer"},{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav"},{"first_name":"Christoph M","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke","orcid":"0000-0003-0201-2315","first_name":"Wiebke","last_name":"Jahr"},{"last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"last_name":"Broichhagen","first_name":"Johannes","full_name":"Broichhagen, Johannes"},{"last_name":"Grant","first_name":"Seth G.N.","full_name":"Grant, Seth G.N."},{"last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Pfister","full_name":"Pfister, Hanspeter","first_name":"Hanspeter"},{"last_name":"Bickel","id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","first_name":"Bernd"},{"last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","first_name":"Johann G"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"citation":{"apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>.","ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>.","ieee":"P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265."},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"ddc":["570"],"publisher":"Springer Nature","page":"1256-1265","oa":1,"language":[{"iso":"eng"}],"volume":20,"publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"file":[{"date_created":"2025-02-26T08:01:57Z","content_type":"application/pdf","access_level":"open_access","checksum":"a68e845780a82ea36d0d4d3212a87c10","relation":"main_file","creator":"dernst","file_id":"19088","success":1,"file_size":14103039,"file_name":"2023_NatureMethods_Velicky.pdf","date_updated":"2025-02-26T08:01:57Z"}],"acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)."},{"ddc":["580"],"publisher":"Elsevier","page":"1533-1542","oa":1,"language":[{"iso":"eng"}],"volume":15,"publication_identifier":{"issn":["1674-2052"]},"file":[{"success":1,"creator":"dernst","file_id":"12435","file_name":"2022_MolecularPlant_Johnson.pdf","date_updated":"2023-01-30T07:46:51Z","file_size":2307251,"content_type":"application/pdf","access_level":"open_access","date_created":"2023-01-30T07:46:51Z","relation":"main_file","checksum":"04d5c12490052d03e4dc4412338a43dd"}],"acknowledgement":"A.J. is supported by funding from the Austrian Science Fund I3630B25 (to J.F.). This research was supported by the Scientific Service Units of Institute of Science and Technology Austria (ISTA) through resources provided by the Electron Microscopy Facility, Lab Support Facility, and the Imaging and Optics Facility. We acknowledge Prof. David Robinson (Heidelberg) and Prof. Jan Traas (Lyon) for making us aware of previously published classical on-grid preparation methods. No conflict of interest declared.","type":"journal_article","issue":"10","author":[{"id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","full_name":"Johnson, Alexander J","orcid":"0000-0002-2739-8843","first_name":"Alexander J","last_name":"Johnson"},{"last_name":"Kaufmann","full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter"},{"last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M"},{"first_name":"Tommaso","id":"D93824F4-D9BA-11E9-BB12-F207E6697425","full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","last_name":"Costanzo"},{"last_name":"Dahhan","full_name":"Dahhan, Dana A.","first_name":"Dana A."},{"last_name":"Bednarek","full_name":"Bednarek, Sebastian Y.","first_name":"Sebastian Y."},{"first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","last_name":"Friml"}],"file_date_updated":"2023-01-30T07:46:51Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"citation":{"ama":"Johnson AJ, Kaufmann W, Sommer CM, et al. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. <i>Molecular Plant</i>. 2022;15(10):1533-1542. doi:<a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">10.1016/j.molp.2022.09.003</a>","ieee":"A. J. Johnson <i>et al.</i>, “Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution,” <i>Molecular Plant</i>, vol. 15, no. 10. Elsevier, pp. 1533–1542, 2022.","short":"A.J. Johnson, W. Kaufmann, C.M. Sommer, T. Costanzo, D.A. Dahhan, S.Y. Bednarek, J. Friml, Molecular Plant 15 (2022) 1533–1542.","ista":"Johnson AJ, Kaufmann W, Sommer CM, Costanzo T, Dahhan DA, Bednarek SY, Friml J. 2022. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. 15(10), 1533–1542.","mla":"Johnson, Alexander J., et al. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” <i>Molecular Plant</i>, vol. 15, no. 10, Elsevier, 2022, pp. 1533–42, doi:<a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">10.1016/j.molp.2022.09.003</a>.","apa":"Johnson, A. J., Kaufmann, W., Sommer, C. M., Costanzo, T., Dahhan, D. A., Bednarek, S. Y., &#38; Friml, J. (2022). Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. <i>Molecular Plant</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">https://doi.org/10.1016/j.molp.2022.09.003</a>","chicago":"Johnson, Alexander J, Walter Kaufmann, Christoph M Sommer, Tommaso Costanzo, Dana A. Dahhan, Sebastian Y. Bednarek, and Jiří Friml. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” <i>Molecular Plant</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">https://doi.org/10.1016/j.molp.2022.09.003</a>."},"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"Bio"}],"date_updated":"2025-04-15T07:32:09Z","quality_controlled":"1","intvolume":"        15","date_published":"2022-10-03T00:00:00Z","publication":"Molecular Plant","pmid":1,"scopus_import":"1","article_processing_charge":"Yes (via OA deal)","fulldoi":"https://doi.org/10.1016/j.molp.2022.09.003","doi":"10.1016/j.molp.2022.09.003","publication_status":"published","article_type":"original","date_created":"2023-01-16T09:51:49Z","year":"2022","has_accepted_license":"1","title":"Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","keyword":["Plant Science","Molecular Biology"],"corr_author":"1","day":"03","month":"10","isi":1,"status":"public","_id":"12239","abstract":[{"lang":"eng","text":"Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs."}],"oa_version":"Published Version","department":[{"_id":"JiFr"},{"_id":"EM-Fac"},{"_id":"Bio"}],"project":[{"grant_number":"I03630","_id":"26538374-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular mechanisms of endocytic cargo recognition in plants"}],"external_id":{"isi":["000882769800009"],"pmid":["36081349"]}},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"citation":{"chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>. Oxford University Press, 2022. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>.","ista":"Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009.","mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009, Oxford University Press, 2022, doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>.","apa":"Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>","short":"A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022).","ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1). doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>","ieee":"A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1. Oxford University Press, 2022."},"author":[{"full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen"},{"last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","first_name":"Florian"},{"last_name":"Riedl","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4844-6311","full_name":"Riedl, Michael"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"last_name":"Heger","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena"},{"first_name":"Susanne","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel"},{"last_name":"Hof","first_name":"Björn","full_name":"Hof, Björn","orcid":"0000-0003-2057-2754","id":"3A374330-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tsai","first_name":"Li Huei","full_name":"Tsai, Li Huei"},{"full_name":"Rülicke, Thomas","first_name":"Thomas","last_name":"Rülicke"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"file_date_updated":"2023-08-16T08:00:30Z","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"type":"journal_article","issue":"1","article_number":"kvac009","publication_identifier":{"eissn":["2753-149X"]},"volume":1,"acknowledgement":"A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility.","file":[{"file_size":4846551,"file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","date_updated":"2023-08-16T08:00:30Z","file_id":"14061","creator":"dernst","success":1,"checksum":"822e76e056c07099d1fb27d1ece5941b","relation":"main_file","content_type":"application/pdf","date_created":"2023-08-16T08:00:30Z","access_level":"open_access"}],"publisher":"Oxford University Press","ddc":["570"],"oa":1,"language":[{"iso":"eng"}],"project":[{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7"},{"name":"Molecular mechanisms of radial neuronal migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812"}],"department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"ec_funded":1,"_id":"10791","abstract":[{"text":"The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general.","lang":"eng"}],"oa_version":"Published Version","external_id":{"pmid":["38596707"]},"title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12726"},{"relation":"dissertation_contains","id":"14530","status":"public"}]},"month":"07","day":"07","status":"public","corr_author":"1","fulldoi":"https://doi.org/10.1093/oons/kvac009","doi":"10.1093/oons/kvac009","article_processing_charge":"No","year":"2022","date_created":"2022-02-25T07:52:11Z","article_type":"original","publication_status":"published","intvolume":"         1","date_updated":"2026-04-07T13:29:13Z","quality_controlled":"1","publication":"Oxford Open Neuroscience","pmid":1,"date_published":"2022-07-07T00:00:00Z"},{"month":"04","day":"05","related_material":{"record":[{"id":"18674","relation":"dissertation_contains","status":"public"},{"status":"public","relation":"dissertation_contains","id":"18681"},{"id":"12364","relation":"dissertation_contains","status":"public"}]},"status":"public","isi":1,"corr_author":"1","keyword":["General Biochemistry","Genetics and Molecular Biology"],"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","external_id":{"isi":["000785983900003"],"pmid":["35385734"]},"project":[{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF"}],"department":[{"_id":"JoDa"},{"_id":"GaNo"}],"_id":"11160","abstract":[{"lang":"eng","text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling."}],"ec_funded":1,"oa_version":"Published Version","publication":"Cell Reports","pmid":1,"date_published":"2022-04-05T00:00:00Z","intvolume":"        39","date_updated":"2026-10-04T22:30:09Z","quality_controlled":"1","year":"2022","date_created":"2022-04-15T09:03:10Z","publication_status":"published","article_type":"original","fulldoi":"https://doi.org/10.1016/j.celrep.2022.110615","doi":"10.1016/j.celrep.2022.110615","scopus_import":"1","article_processing_charge":"Yes","type":"journal_article","issue":"1","article_number":"110615","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"citation":{"short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"author":[{"full_name":"Villa, Carlo Emanuele","first_name":"Carlo Emanuele","last_name":"Villa"},{"first_name":"Cristina","full_name":"Cheroni, Cristina","last_name":"Cheroni"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","first_name":"Christoph","last_name":"Dotter"},{"full_name":"López-Tóbon, Alejandro","first_name":"Alejandro","last_name":"López-Tóbon"},{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","first_name":"Bárbara","last_name":"Oliveira"},{"last_name":"Sacco","full_name":"Sacco, Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto"},{"full_name":"Yahya, Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","first_name":"Aysan Çerağ","last_name":"Yahya"},{"last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","first_name":"Jasmin"},{"full_name":"Gabriele, Michele","first_name":"Michele","last_name":"Gabriele"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854","first_name":"Mojtaba","last_name":"Tavakoli"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik"},{"last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"first_name":"Mariano","full_name":"Gabitto, Mariano","last_name":"Gabitto"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl"},{"last_name":"Testa","full_name":"Testa, Giuseppe","first_name":"Giuseppe"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino"}],"file_date_updated":"2022-04-15T09:06:25Z","oa":1,"language":[{"iso":"eng"}],"publisher":"Elsevier","ddc":["570"],"acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","file":[{"success":1,"file_id":"11164","creator":"dernst","file_name":"2022_CellReports_Villa.pdf","date_updated":"2022-04-15T09:06:25Z","file_size":"7808644","content_type":"application/pdf","date_created":"2022-04-15T09:06:25Z","access_level":"open_access","relation":"main_file","checksum":"b4e8d68f0268dec499af333e6fd5d8e1"}],"publication_identifier":{"issn":["2211-1247"]},"volume":39},{"publication":"Nature Communications","date_published":"2022-05-12T00:00:00Z","intvolume":"        13","quality_controlled":"1","date_updated":"2026-10-04T22:30:10Z","year":"2022","article_type":"original","date_created":"2022-05-13T09:06:28Z","publication_status":"published","doi":"10.1038/s41467-022-30301-y","fulldoi":"https://doi.org/10.1038/s41467-022-30301-y","scopus_import":"1","article_processing_charge":"No","status":"public","isi":1,"month":"05","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41467-022-34485-1"}],"record":[{"status":"public","relation":"research_data","id":"10934"},{"id":"14280","relation":"dissertation_contains","status":"public"}]},"day":"12","corr_author":"1","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"In vitro reconstitution of Escherichia coli divisome activation","has_accepted_license":"1","external_id":{"isi":["000795171100037"]},"project":[{"_id":"2595697A-B435-11E9-9278-68D0E5697425","grant_number":"679239","name":"Self-Organization of the Bacterial Cell","call_identifier":"H2020"},{"name":"In vitro reconstitution of bacterial cell division","_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","grant_number":"P34607"}],"department":[{"_id":"MaLo"}],"oa_version":"Published Version","_id":"11373","abstract":[{"lang":"eng","text":"The actin-homologue FtsA is essential for E. coli cell division, as it links FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate cell constriction by switching from an inactive polymeric to an active monomeric conformation, which recruits downstream proteins and stabilizes the Z-ring. However, direct biochemical evidence for this mechanism is missing. Here, we use reconstitution experiments and quantitative fluorescence microscopy to study divisome activation in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament stabilization and recruitment of FtsN. We could attribute these differences to a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction. We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer that follows treadmilling filaments of FtsZ."}],"ec_funded":1,"language":[{"iso":"eng"}],"oa":1,"publisher":"Springer Nature","ddc":["570"],"acknowledgement":"We acknowledge members of the Loose laboratory at IST Austria for helpful discussions—in particular L. Lindorfer for his assistance with cloning and purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski (Lehigh University, Bethlehem, PA, USA) and S. Martin (University of Lausanne, Switzerland) for sharing their code for FRAP analysis. We are also thankful for the support by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4 to N.B. For the purpose of open access, we have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","file":[{"file_name":"2022_NatureCommunications_Radler.pdf","date_updated":"2022-05-13T09:10:51Z","file_size":6945191,"success":1,"creator":"dernst","file_id":"11374","relation":"main_file","checksum":"5af863ee1b95a0710f6ee864d68dc7a6","date_created":"2022-05-13T09:10:51Z","access_level":"open_access","content_type":"application/pdf"}],"publication_identifier":{"issn":["2041-1723"]},"volume":13,"type":"journal_article","article_number":"2635","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"citation":{"chicago":"Radler, Philipp, Natalia S. Baranova, Paulo R Dos Santos Caldas, Christoph M Sommer, Maria D Lopez Pelegrin, David Michalik, and Martin Loose. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-30301-y\">https://doi.org/10.1038/s41467-022-30301-y</a>.","ista":"Radler P, Baranova NS, Dos Santos Caldas PR, Sommer CM, Lopez Pelegrin MD, Michalik D, Loose M. 2022. In vitro reconstitution of Escherichia coli divisome activation. Nature Communications. 13, 2635.","mla":"Radler, Philipp, et al. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>, vol. 13, 2635, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-30301-y\">10.1038/s41467-022-30301-y</a>.","apa":"Radler, P., Baranova, N. S., Dos Santos Caldas, P. R., Sommer, C. M., Lopez Pelegrin, M. D., Michalik, D., &#38; Loose, M. (2022). In vitro reconstitution of Escherichia coli divisome activation. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-30301-y\">https://doi.org/10.1038/s41467-022-30301-y</a>","short":"P. Radler, N.S. Baranova, P.R. Dos Santos Caldas, C.M. Sommer, M.D. Lopez Pelegrin, D. Michalik, M. Loose, Nature Communications 13 (2022).","ama":"Radler P, Baranova NS, Dos Santos Caldas PR, et al. In vitro reconstitution of Escherichia coli divisome activation. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-30301-y\">10.1038/s41467-022-30301-y</a>","ieee":"P. Radler <i>et al.</i>, “In vitro reconstitution of Escherichia coli divisome activation,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"file_date_updated":"2022-05-13T09:10:51Z","author":[{"id":"40136C2A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9198-2182 ","full_name":"Radler, Philipp","first_name":"Philipp","last_name":"Radler"},{"id":"38661662-F248-11E8-B48F-1D18A9856A87","full_name":"Baranova, Natalia S.","orcid":"0000-0002-3086-9124","first_name":"Natalia S.","last_name":"Baranova"},{"first_name":"Paulo R","full_name":"Dos Santos Caldas, Paulo R","orcid":"0000-0001-6730-4461","id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87","last_name":"Dos Santos Caldas"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"full_name":"Lopez Pelegrin, Maria D","id":"319AA9CE-F248-11E8-B48F-1D18A9856A87","first_name":"Maria D","last_name":"Lopez Pelegrin"},{"first_name":"David","id":"B9577E20-AA38-11E9-AC9A-0930E6697425","full_name":"Michalik, David","last_name":"Michalik"},{"first_name":"Martin","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","last_name":"Loose"}]},{"abstract":[{"text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full <jats:italic>in-silico</jats:italic> reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches<jats:sup>6–12</jats:sup> facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy<jats:sup>6,13</jats:sup> in extracellularly labelled tissue<jats:sup>14</jats:sup> for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue.","lang":"eng"}],"_id":"11943","author":[{"first_name":"Philipp","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky"},{"last_name":"Miguel Villalba","orcid":"0000-0001-5665-0430","full_name":"Miguel Villalba, Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder"},{"first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska"},{"last_name":"Wei","full_name":"Wei, Donglai","first_name":"Donglai"},{"last_name":"Lin","first_name":"Zudi","full_name":"Lin, Zudi"},{"last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"first_name":"Jakob","full_name":"Troidl, Jakob","last_name":"Troidl"},{"last_name":"Beyer","full_name":"Beyer, Johanna","first_name":"Johanna"},{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav"},{"last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jahr","first_name":"Wiebke","orcid":"0000-0003-0201-2315","full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alban","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri"},{"last_name":"Broichhagen","first_name":"Johannes","full_name":"Broichhagen, Johannes"},{"full_name":"Grant, Seth G. N.","first_name":"Seth G. N.","last_name":"Grant"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas"},{"last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia"},{"last_name":"Pfister","first_name":"Hanspeter","full_name":"Pfister, Hanspeter"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385","first_name":"Bernd","last_name":"Bickel"},{"last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G"}],"oa_version":"Preprint","citation":{"chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>.","ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, <a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>","ieee":"P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,” <i>bioRxiv</i>. ."},"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"corr_author":"1","related_material":{"record":[{"status":"public","id":"13267","relation":"later_version"},{"id":"12470","relation":"dissertation_contains","status":"public"}]},"month":"05","day":"09","status":"public","OA_place":"repository","main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"title":"Saturated reconstruction of living brain tissue","type":"preprint","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","das_tickbox":"1","publication_status":"draft","date_created":"2022-08-23T11:07:59Z","year":"2022","article_processing_charge":"No","fulldoi":"https://doi.org/10.1101/2022.03.16.484431","doi":"10.1101/2022.03.16.484431","date_published":"2022-05-09T00:00:00Z","publication":"bioRxiv","oa":1,"language":[{"iso":"eng"}],"date_updated":"2026-10-04T22:31:02Z"},{"_id":"11950","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons.","lang":"eng"}],"author":[{"last_name":"Michalska","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik"},{"last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp"},{"first_name":"Hana","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","first_name":"Jake","last_name":"Watson"},{"first_name":"Alban","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","last_name":"Venturino"},{"last_name":"Roessler","first_name":"Karl","full_name":"Roessler, Karl"},{"full_name":"Czech, Thomas","first_name":"Thomas","last_name":"Czech"},{"last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"},{"last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G"}],"oa_version":"Preprint","citation":{"ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>","ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. .","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.)."},"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"corr_author":"1","related_material":{"record":[{"status":"public","id":"12470","relation":"dissertation_contains"}]},"month":"08","day":"18","status":"public","main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"type":"preprint","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","das_tickbox":"1","publication_status":"draft","date_created":"2022-08-24T08:24:52Z","year":"2022","article_processing_charge":"No","fulldoi":"https://doi.org/10.1101/2022.08.17.504272","doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","publication":"bioRxiv","language":[{"iso":"eng"}],"oa":1,"date_updated":"2026-10-04T22:31:02Z"},{"oa":1,"language":[{"iso":"eng"}],"ddc":["610"],"publisher":"Embo Press","file":[{"checksum":"78d2d02e775322297e774f72810a41a4","relation":"main_file","access_level":"open_access","date_created":"2021-12-13T14:54:14Z","content_type":"application/pdf","file_size":7819881,"date_updated":"2021-12-13T14:54:14Z","file_name":"2021_EMBO_Bajaj.pdf","file_id":"10541","creator":"alisjak","success":1}],"acknowledgement":"We thank all Knoblich laboratory members for continued support and discussions. We thank the IMP/IMBA BioOptics facility, particularly Pawel Pasierbek, Alberto Moreno Cencerrado and Gerald Schmauss, the IMP/IMBA Molecular Biology Service, in particular Robert Heinen, the IMP Bioinformatics facility, in particular Thomas Burkard, the Vienna Biocenter Core Facilities (VBCF) Histopathology facility, in particular Tamara Engelmaier, and the VBCF Next Generation Sequencing Facility, notably Volodymyr Shubchynskyy and Carmen Czepe. We would also like to thank Simon Haendeler for advice on statistical analyses, Jose Guzman for discussions and assistance with slice culture setups, Oliver L. Eichmueller for discussions and assistance with microscopy, and E.H. Gustafson, S. Wolfinger, and D. Reumann for technical assistance regarding generation of cerebral organoids. This project received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie fellowship agreement Nr.707109 awarded to J.A.B. Work in J.A.K.'s laboratory is supported by the Austrian Federal Ministry of Education, Science and Research, the Austrian Academy of Sciences, the City of Vienna, a Research Program of the Austrian Science Fund FWF (SFBF78 Stem Cell, F 7803-B) and a European Research Council (ERC) Advanced Grant under the European 20 Union’s Horizon 2020 program (grant agreement no. 695642).","volume":40,"publication_identifier":{"eissn":["1460-2075"],"issn":["0261-4189"]},"article_number":"e108714","type":"journal_article","issue":"23","author":[{"last_name":"Bajaj","full_name":"Bajaj, Sunanjay","first_name":"Sunanjay"},{"last_name":"Bagley","first_name":"Joshua A.","full_name":"Bagley, Joshua A."},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer"},{"first_name":"Abel","full_name":"Vertesy, Abel","last_name":"Vertesy"},{"full_name":"Nagumo Wong, Sakurako","first_name":"Sakurako","last_name":"Nagumo Wong"},{"last_name":"Krenn","full_name":"Krenn, Veronica","first_name":"Veronica"},{"first_name":"Julie","full_name":"Lévi-Strauss, Julie","last_name":"Lévi-Strauss"},{"last_name":"Knoblich","first_name":"Juergen A.","full_name":"Knoblich, Juergen A."}],"file_date_updated":"2021-12-13T14:54:14Z","citation":{"mla":"Bajaj, Sunanjay, et al. “Neurotransmitter Signaling Regulates Distinct Phases of Multimodal Human Interneuron Migration.” <i>EMBO Journal</i>, vol. 40, no. 23, e108714, Embo Press, 2021, doi:<a href=\"https://doi.org/10.15252/embj.2021108714\">10.15252/embj.2021108714</a>.","ista":"Bajaj S, Bagley JA, Sommer CM, Vertesy A, Nagumo Wong S, Krenn V, Lévi-Strauss J, Knoblich JA. 2021. Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. EMBO Journal. 40(23), e108714.","apa":"Bajaj, S., Bagley, J. A., Sommer, C. M., Vertesy, A., Nagumo Wong, S., Krenn, V., … Knoblich, J. A. (2021). Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. <i>EMBO Journal</i>. Embo Press. <a href=\"https://doi.org/10.15252/embj.2021108714\">https://doi.org/10.15252/embj.2021108714</a>","chicago":"Bajaj, Sunanjay, Joshua A. Bagley, Christoph M Sommer, Abel Vertesy, Sakurako Nagumo Wong, Veronica Krenn, Julie Lévi-Strauss, and Juergen A. Knoblich. “Neurotransmitter Signaling Regulates Distinct Phases of Multimodal Human Interneuron Migration.” <i>EMBO Journal</i>. Embo Press, 2021. <a href=\"https://doi.org/10.15252/embj.2021108714\">https://doi.org/10.15252/embj.2021108714</a>.","ieee":"S. Bajaj <i>et al.</i>, “Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration,” <i>EMBO Journal</i>, vol. 40, no. 23. Embo Press, 2021.","ama":"Bajaj S, Bagley JA, Sommer CM, et al. Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. <i>EMBO Journal</i>. 2021;40(23). doi:<a href=\"https://doi.org/10.15252/embj.2021108714\">10.15252/embj.2021108714</a>","short":"S. Bajaj, J.A. Bagley, C.M. Sommer, A. Vertesy, S. Nagumo Wong, V. Krenn, J. Lévi-Strauss, J.A. Knoblich, EMBO Journal 40 (2021)."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"date_published":"2021-10-18T00:00:00Z","publication":"EMBO Journal","pmid":1,"quality_controlled":"1","date_updated":"2023-08-14T08:05:23Z","intvolume":"        40","publication_status":"published","article_type":"original","date_created":"2021-10-24T22:01:34Z","year":"2021","article_processing_charge":"Yes (in subscription journal)","scopus_import":"1","fulldoi":"https://doi.org/10.15252/embj.2021108714","doi":"10.15252/embj.2021108714","month":"10","day":"18","isi":1,"status":"public","has_accepted_license":"1","title":"Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000708012800001"],"pmid":["34661293"]},"_id":"10179","abstract":[{"text":"Inhibitory GABAergic interneurons migrate over long distances from their extracortical origin into the developing cortex. In humans, this process is uniquely slow and prolonged, and it is unclear whether guidance cues unique to humans govern the various phases of this complex developmental process. Here, we use fused cerebral organoids to identify key roles of neurotransmitter signaling pathways in guiding the migratory behavior of human cortical interneurons. We use scRNAseq to reveal expression of GABA, glutamate, glycine, and serotonin receptors along distinct maturation trajectories across interneuron migration. We develop an image analysis software package, TrackPal, to simultaneously assess 48 parameters for entire migration tracks of individual cells. By chemical screening, we show that different modes of interneuron migration depend on distinct neurotransmitter signaling pathways, linking transcriptional maturation of interneurons with their migratory behavior. Altogether, our study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by neurotransmitter signaling.","lang":"eng"}],"oa_version":"Published Version","department":[{"_id":"Bio"}]},{"issue":"1","type":"journal_article","article_number":"3058","acknowledged_ssus":[{"_id":"PreCl"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"citation":{"chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>"},"author":[{"last_name":"Morandell","first_name":"Jasmin","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A","last_name":"Schwarz"},{"first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","last_name":"Basilico"},{"orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","last_name":"Tasciyan"},{"full_name":"Dimchev, Georgi A","orcid":"0000-0001-8370-6161","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","first_name":"Georgi A","last_name":"Dimchev"},{"last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","first_name":"Armel"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer"},{"first_name":"Caroline","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger"},{"last_name":"Dotter","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph"},{"first_name":"Lisa","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus"},{"first_name":"Zoe","full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","last_name":"Dobler"},{"full_name":"Cacci, Emanuele","first_name":"Emanuele","last_name":"Cacci"},{"id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","first_name":"Florian KM","last_name":"Schur"},{"last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino"}],"file_date_updated":"2021-05-28T12:39:43Z","language":[{"iso":"eng"}],"oa":1,"publisher":"Springer Nature","ddc":["572"],"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","file":[{"file_size":9358599,"date_updated":"2021-05-28T12:39:43Z","file_name":"2021_NatureCommunications_Morandell.pdf","creator":"kschuh","file_id":"9430","success":1,"checksum":"337e0f7959c35ec959984cacdcb472ba","relation":"main_file","content_type":"application/pdf","date_created":"2021-05-28T12:39:43Z","access_level":"open_access"}],"publication_identifier":{"eissn":["2041-1723"]},"volume":12,"month":"05","day":"24","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"19557"},{"status":"public","id":"7800","relation":"earlier_version"},{"status":"public","id":"12401","relation":"dissertation_contains"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/"}]},"status":"public","isi":1,"keyword":["General Biochemistry","Genetics and Molecular Biology"],"corr_author":"1","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","has_accepted_license":"1","external_id":{"isi":["000658769900010"]},"department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F7807"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"}],"_id":"9429","ec_funded":1,"abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.","lang":"eng"}],"oa_version":"Published Version","publication":"Nature Communications","date_published":"2021-05-24T00:00:00Z","intvolume":"        12","date_updated":"2026-10-04T22:30:15Z","quality_controlled":"1","year":"2021","article_type":"original","publication_status":"published","date_created":"2021-05-28T11:49:46Z","fulldoi":"https://doi.org/10.1038/s41467-021-23123-x","doi":"10.1038/s41467-021-23123-x","article_processing_charge":"No","scopus_import":"1"},{"quality_controlled":"1","date_updated":"2026-04-08T07:26:30Z","intvolume":"       158","date_published":"2020-02-27T00:00:00Z","publication":"Methods in Cell Biology","article_processing_charge":"No","scopus_import":"1","fulldoi":"https://doi.org/10.1016/bs.mcb.2020.01.006","doi":"10.1016/bs.mcb.2020.01.006","date_created":"2020-03-08T23:00:47Z","publication_status":"published","year":"2020","title":"Computational analysis of filament polymerization dynamics in cytoskeletal networks","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"27","month":"02","related_material":{"record":[{"relation":"part_of_dissertation","id":"8358","status":"public"}]},"status":"public","isi":1,"ec_funded":1,"_id":"7572","abstract":[{"lang":"eng","text":"The polymerization–depolymerization dynamics of cytoskeletal proteins play essential roles in the self-organization of cytoskeletal structures, in eukaryotic as well as prokaryotic cells. While advances in fluorescence microscopy and in vitro reconstitution experiments have helped to study the dynamic properties of these complex systems, methods that allow to collect and analyze large quantitative datasets of the underlying polymer dynamics are still missing. Here, we present a novel image analysis workflow to study polymerization dynamics of active filaments in a nonbiased, highly automated manner. Using treadmilling filaments of the bacterial tubulin FtsZ as an example, we demonstrate that our method is able to specifically detect, track and analyze growth and shrinkage of polymers, even in dense networks of filaments. We believe that this automated method can facilitate the analysis of a large variety of dynamic cytoskeletal systems, using standard time-lapse movies obtained from experiments in vitro as well as in the living cell. Moreover, we provide scripts implementing this method as supplementary material."}],"oa_version":"Preprint","project":[{"_id":"2595697A-B435-11E9-9278-68D0E5697425","grant_number":"679239","name":"Self-Organization of the Bacterial Cell","call_identifier":"H2020"},{"_id":"260D98C8-B435-11E9-9278-68D0E5697425","name":"Reconstitution of Bacterial Cell Division Using Purified Components"}],"department":[{"_id":"MaLo"}],"editor":[{"last_name":"Tran","full_name":"Tran, Phong ","first_name":"Phong "}],"alternative_title":["Methods in Cell Biology"],"external_id":{"isi":["000611826500008"]},"publisher":"Elsevier","page":"145-161","language":[{"iso":"eng"}],"oa":1,"volume":158,"publication_identifier":{"issn":["0091-679X"]},"main_file_link":[{"url":"https://doi.org/10.1101/839571","open_access":"1"}],"type":"book_chapter","author":[{"id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87","full_name":"Dos Santos Caldas, Paulo R","orcid":"0000-0001-6730-4461","first_name":"Paulo R","last_name":"Dos Santos Caldas"},{"first_name":"Philipp","orcid":"0000-0001-9198-2182 ","full_name":"Radler, Philipp","id":"40136C2A-F248-11E8-B48F-1D18A9856A87","last_name":"Radler"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"first_name":"Martin","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","last_name":"Loose"}],"citation":{"apa":"Dos Santos Caldas, P. R., Radler, P., Sommer, C. M., &#38; Loose, M. (2020). Computational analysis of filament polymerization dynamics in cytoskeletal networks. In P. Tran (Ed.), <i>Methods in Cell Biology</i> (Vol. 158, pp. 145–161). Elsevier. <a href=\"https://doi.org/10.1016/bs.mcb.2020.01.006\">https://doi.org/10.1016/bs.mcb.2020.01.006</a>","mla":"Dos Santos Caldas, Paulo R., et al. “Computational Analysis of Filament Polymerization Dynamics in Cytoskeletal Networks.” <i>Methods in Cell Biology</i>, edited by Phong  Tran, vol. 158, Elsevier, 2020, pp. 145–61, doi:<a href=\"https://doi.org/10.1016/bs.mcb.2020.01.006\">10.1016/bs.mcb.2020.01.006</a>.","ista":"Dos Santos Caldas PR, Radler P, Sommer CM, Loose M. 2020.Computational analysis of filament polymerization dynamics in cytoskeletal networks. In: Methods in Cell Biology. Methods in Cell Biology, vol. 158, 145–161.","chicago":"Dos Santos Caldas, Paulo R, Philipp Radler, Christoph M Sommer, and Martin Loose. “Computational Analysis of Filament Polymerization Dynamics in Cytoskeletal Networks.” In <i>Methods in Cell Biology</i>, edited by Phong  Tran, 158:145–61. Elsevier, 2020. <a href=\"https://doi.org/10.1016/bs.mcb.2020.01.006\">https://doi.org/10.1016/bs.mcb.2020.01.006</a>.","ama":"Dos Santos Caldas PR, Radler P, Sommer CM, Loose M. Computational analysis of filament polymerization dynamics in cytoskeletal networks. In: Tran P, ed. <i>Methods in Cell Biology</i>. Vol 158. Elsevier; 2020:145-161. doi:<a href=\"https://doi.org/10.1016/bs.mcb.2020.01.006\">10.1016/bs.mcb.2020.01.006</a>","ieee":"P. R. Dos Santos Caldas, P. Radler, C. M. Sommer, and M. Loose, “Computational analysis of filament polymerization dynamics in cytoskeletal networks,” in <i>Methods in Cell Biology</i>, vol. 158, P. Tran, Ed. Elsevier, 2020, pp. 145–161.","short":"P.R. Dos Santos Caldas, P. Radler, C.M. Sommer, M. Loose, in:, P. Tran (Ed.), Methods in Cell Biology, Elsevier, 2020, pp. 145–161."}},{"department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"project":[{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.","lang":"eng"}],"_id":"7800","oa_version":"Preprint","related_material":{"record":[{"status":"public","id":"9429","relation":"later_version"},{"status":"public","id":"8620","relation":"dissertation_contains"}]},"day":"11","month":"01","status":"public","corr_author":"1","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","year":"2020","publication_status":"draft","date_created":"2020-05-05T14:31:33Z","fulldoi":"https://doi.org/10.1101/2020.01.10.902064 ","doi":"10.1101/2020.01.10.902064 ","article_processing_charge":"No","publication":"bioRxiv","date_published":"2020-01-11T00:00:00Z","date_updated":"2026-10-04T22:31:09Z","acknowledged_ssus":[{"_id":"PreCl"}],"citation":{"short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>bioRxiv</i>. .","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>.","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>"},"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"author":[{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A","first_name":"Lena A"},{"last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","first_name":"Bernadette"},{"last_name":"Tasciyan","first_name":"Saren","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","first_name":"Caroline"},{"last_name":"Knaus","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa"},{"last_name":"Dobler","full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe"},{"first_name":"Emanuele","full_name":"Cacci, Emanuele","last_name":"Cacci"},{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"file_date_updated":"2020-07-14T12:48:03Z","type":"preprint","das_tickbox":"1","file":[{"file_id":"7801","creator":"rsix","date_updated":"2020-07-14T12:48:03Z","file_name":"2020.01.10.902064v1.full.pdf","file_size":2931370,"date_created":"2020-05-05T14:31:19Z","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"c6799ab5daba80efe8e2ed63c15f8c81"}],"language":[{"iso":"eng"}],"oa":1,"ddc":["570"]}]