[{"department":[{"_id":"AnKi"},{"_id":"GaNo"},{"_id":"TiVo"},{"_id":"ScienComp"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"PreCl"}],"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).","PlanS_conform":"1","year":"2026","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).","OA_type":"hybrid","researchdata_availability":"yes","quality_controlled":"1","fulldoi":"https://doi.org/10.1038/s41586-026-10679-1","pmid":1,"day":"17","date_updated":"2026-08-04T09:29:55Z","ddc":["570"],"scopus_import":"1","has_accepted_license":"1","status":"public","type":"journal_article","project":[{"_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","grant_number":"101044865"},{"_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964","name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232"},{"name":"Neurobiology of anxiety in autism spectrum disorders","grant_number":"FG1803 49015","_id":"ebb38b5d-77a9-11ec-83b8-a42e08120a88"}],"citation":{"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>.","ieee":"L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026.","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.","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).","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>","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>.","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>"},"publication":"Nature","related_material":{"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/patterns-in-genetic-chaos/","relation":"press_release"}]},"language":[{"iso":"eng"}],"corr_author":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","abstract":[{"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.","lang":"eng"}],"author":[{"full_name":"Schwarz, Lena A","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz"},{"last_name":"Dotter","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph","full_name":"Dotter, Christoph"},{"full_name":"Isaev, Sergey","first_name":"Sergey","last_name":"Isaev"},{"id":"39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c","full_name":"Lisi, Michela","first_name":"Michela","last_name":"Lisi"},{"last_name":"Malzl","first_name":"Daniel","full_name":"Malzl, Daniel"},{"last_name":"Büschl","first_name":"Christoph","full_name":"Büschl, Christoph","id":"2a8c054c-0913-11ee-9159-f8ef515809ed"},{"last_name":"Ladstätter","first_name":"Sabrina","full_name":"Ladstätter, Sabrina"},{"last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara","full_name":"Oliveira, Bárbara"},{"full_name":"Barel, Matteo","first_name":"Matteo","id":"8959927b-2236-11ed-bd6e-ea83d94ade0e","last_name":"Barel"},{"first_name":"Bernadette","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico"},{"last_name":"Chintaluri","orcid":"0000-0003-4252-1608","id":"BA06AFEE-A4BA-11EA-AE5C-14673DDC885E","first_name":"Chaitanya","full_name":"Chintaluri, Chaitanya"},{"last_name":"Gorkiewicz","first_name":"Sarah","full_name":"Gorkiewicz, Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f"},{"last_name":"Goudarzi","first_name":"Mohammad","full_name":"Goudarzi, Mohammad","id":"3384113A-F248-11E8-B48F-1D18A9856A87"},{"id":"0bf89b6a-d28b-11eb-8bd6-f43768e4d368","first_name":"Tereza","full_name":"Belinova, Tereza","last_name":"Belinova"},{"last_name":"Reichl","first_name":"Stephan","full_name":"Reichl, Stephan"},{"last_name":"Sendžikaitė","full_name":"Sendžikaitė, Gintarė","first_name":"Gintarė","id":"dd6d52f2-c50d-11eb-9548-bcf0ff82b344"},{"orcid":"0000-0002-2479-2669","id":"b0bbee33-09f7-11eb-909c-8b358058d28a","first_name":"Satish","full_name":"Arcot Jayaram, Satish","last_name":"Arcot Jayaram"},{"last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","first_name":"Peter"},{"last_name":"Sommer","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"orcid":"0000-0003-3295-6181","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425","full_name":"Vogels, Tim P","first_name":"Tim P","last_name":"Vogels"},{"last_name":"Menche","first_name":"Jörg","full_name":"Menche, Jörg"},{"first_name":"Igor","full_name":"Adameyko, Igor","last_name":"Adameyko"},{"last_name":"Kharchenko","first_name":"Peter Vasili","full_name":"Kharchenko, Peter Vasili","id":"0095641e-7eb7-11f1-8665-aec51a2ab5e0"},{"last_name":"Bock","first_name":"Christoph","full_name":"Bock, Christoph"},{"full_name":"Novarino, Gaia","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino"}],"external_id":{"pmid":["42310454"]},"publication_status":"epub_ahead","date_created":"2026-07-13T09:47:21Z","article_processing_charge":"Yes (via OA deal)","doi":"10.1038/s41586-026-10679-1","oa_version":"Published Version","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"publisher":"Springer Nature","_id":"22295","supplementarymaterial":"yes","title":"Cortical development dynamics across autism spectrum disorder mouse models","article_type":"original","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41586-026-10679-1"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"date_published":"2026-06-17T00:00:00Z","OA_place":"publisher","oa":1,"month":"06"},{"language":[{"iso":"eng"}],"related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/piecing-together-the-brain-puzzle/"}],"record":[{"id":"18697","status":"public","relation":"research_data"},{"relation":"earlier_version","status":"public","id":"18677"}]},"isi":1,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","corr_author":"1","publication":"Nature","intvolume":"       642","citation":{"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>","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>.","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.","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.","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>.","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.","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>"},"date_created":"2025-05-18T22:02:51Z","doi":"10.1038/s41586-025-08985-1","article_processing_charge":"Yes (via OA deal)","publication_status":"published","oa_version":"Published Version","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"file_date_updated":"2025-07-03T06:55:20Z","external_id":{"isi":["001483477000001"],"pmid":["40335689"]},"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 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."}],"author":[{"first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","last_name":"Tavakoli"},{"last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia"},{"first_name":"Michał","full_name":"Januszewski, Michał","last_name":"Januszewski"},{"id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","first_name":"Vitali","full_name":"Vistunou, Vitali","last_name":"Vistunou"},{"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","first_name":"Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425","orcid":"0009-0000-7590-3501"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"last_name":"Kreuzinger","first_name":"Caroline","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara","full_name":"Oliveira, Bárbara","last_name":"Oliveira"},{"last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","first_name":"Alban"},{"last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jain","full_name":"Jain, Viren","first_name":"Viren"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl"}],"title":"Light-microscopy-based connectomic reconstruction of mammalian brain tissue","article_type":"original","publisher":"Springer Nature","_id":"19704","oa":1,"date_published":"2025-06-12T00:00:00Z","OA_place":"publisher","month":"06","volume":642,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"department":[{"_id":"JoDa"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"GaNo"}],"year":"2025","PlanS_conform":"1","file":[{"file_size":133201290,"access_level":"open_access","date_created":"2025-07-03T06:55:20Z","file_id":"19959","checksum":"ebc99d7108e728f46db0a009292675ef","success":1,"content_type":"application/pdf","relation":"main_file","file_name":"2025_Nature_Tavakoli.pdf","creator":"dernst","date_updated":"2025-07-03T06:55:20Z"}],"quality_controlled":"1","OA_type":"hybrid","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).","ddc":["570"],"scopus_import":"1","day":"12","date_updated":"2026-10-02T09:59:44Z","fulldoi":"https://doi.org/10.1038/s41586-025-08985-1","pmid":1,"project":[{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","grant_number":"26137"},{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","grant_number":"101044865","name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders"},{"_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF"}],"page":"398-410","ec_funded":1,"status":"public","has_accepted_license":"1","type":"journal_article"},{"publisher":"Institute of Science and Technology Austria","_id":"19557","title":"Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"ScienComp"}],"date_published":"2025-04-14T00:00:00Z","OA_place":"publisher","oa":1,"month":"04","citation":{"apa":"Schwarz, L. A. (2025). <i>Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-19557\">https://doi.org/10.15479/AT-ISTA-19557</a>","mla":"Schwarz, Lena A. <i>Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19557\">10.15479/AT-ISTA-19557</a>.","ama":"Schwarz LA. Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19557\">10.15479/AT-ISTA-19557</a>","short":"L.A. Schwarz, Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution, Institute of Science and Technology Austria, 2025.","ista":"Schwarz LA. 2025. Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution. Institute of Science and Technology Austria.","ieee":"L. A. Schwarz, “Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution,” Institute of Science and Technology Austria, 2025.","chicago":"Schwarz, Lena A. “Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-19557\">https://doi.org/10.15479/AT-ISTA-19557</a>."},"related_material":{"record":[{"id":"12802","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"9429"}]},"language":[{"iso":"eng"}],"corr_author":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file_date_updated":"2026-10-15T22:30:02Z","author":[{"last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A","full_name":"Schwarz, Lena A"}],"doi":"10.15479/AT-ISTA-19557","article_processing_charge":"No","date_created":"2025-04-14T06:59:06Z","publication_status":"published","oa_version":"Published Version","publication_identifier":{"issn":["2663-337X"]},"fulldoi":"https://doi.org/10.15479/AT-ISTA-19557","day":"14","date_updated":"2026-10-15T22:30:03Z","ddc":["570"],"has_accepted_license":"1","status":"public","type":"dissertation","page":"124","project":[{"grant_number":"707964","name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A"},{"_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","grant_number":"101044865","name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders"},{"grant_number":"W1232","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"degree_awarded":"PhD","alternative_title":["ISTA Thesis"],"department":[{"_id":"GradSch"},{"_id":"GaNo"}],"file":[{"date_updated":"2026-10-15T22:30:02Z","creator":"lschwarz","file_name":"Schwarz_Thesis_2025_FINAL.docx","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","checksum":"50290a8604edb0a720387f01e9d59fe4","file_id":"19561","access_level":"closed","date_created":"2025-04-15T08:43:36Z","file_size":21783427},{"content_type":"application/pdf","relation":"main_file","file_name":"Schwarz_Thesis_2025_FINALpdfa.pdf","creator":"lschwarz","embargo":"2026-10-15","date_updated":"2026-10-15T22:30:02Z","file_size":11432175,"access_level":"open_access","file_id":"19562","date_created":"2025-04-15T08:43:42Z","checksum":"ed028488180ac4901e018ef1c330cf01"}],"supervisor":[{"last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"year":"2025","acknowledgement":"The work presented in this doctoral thesis was performed at the Institute of Science\r\nand Technology (ISTA) and financially supported by a European Research Council\r\n(ERC) Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02) and by the\r\nAustrian Science Fund (FWF) to Gaia Novarino (PE1028W1232). I am very thankful\r\nto the Doctoral Program “Molecular Drug Targets” (MolTag) for offering me financial\r\nsupport to perform essential experiments during my PhD studies and to participate in\r\ninternational conferences and courses."},{"supplementarymaterial":"no","_id":"18677","main_file_link":[{"url":"https://doi.org/10.1101/2024.03.01.582884","open_access":"1"}],"title":"Light-microscopy based dense connectomic reconstruction of mammalian brain tissue","acknowledged_ssus":[{"_id":"E-Lib"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"ScienComp"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","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)"},"month":"07","oa":1,"OA_place":"repository","date_published":"2024-07-08T00:00:00Z","das_tickbox":"0","publication":"bioRxiv","citation":{"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>","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>.","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>","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.).","ieee":"M. Tavakoli <i>et al.</i>, “Light-microscopy based dense connectomic reconstruction of mammalian brain tissue,” <i>bioRxiv</i>. .","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>.","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>."},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"later_version","id":"19704","status":"public"},{"id":"18674","status":"public","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"18681"}]},"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."}],"author":[{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","full_name":"Tavakoli, Mojtaba","first_name":"Mojtaba","last_name":"Tavakoli"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik"},{"last_name":"Januszewski","first_name":"Michał","full_name":"Januszewski, Michał"},{"first_name":"Vitali","full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","last_name":"Vistunou"},{"full_name":"Agudelo Duenas, Nathalie","first_name":"Nathalie","id":"40E7F008-F248-11E8-B48F-1D18A9856A87","last_name":"Agudelo Duenas"},{"id":"937696FA-C996-11E9-8C7C-CF13E6697425","orcid":"0009-0000-7590-3501","first_name":"Jakob","full_name":"Vorlaufer, Jakob","last_name":"Vorlaufer"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kreuzinger","first_name":"Caroline","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Oliveira, Bárbara","first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","last_name":"Oliveira"},{"last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","first_name":"Alban"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Jain, Viren","first_name":"Viren","last_name":"Jain"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl"}],"oa_version":"Preprint","doi":"10.1101/2024.03.01.582884","article_processing_charge":"No","publication_status":"draft","date_created":"2024-12-18T14:48:24Z","date_updated":"2026-10-02T11:27:43Z","day":"08","fulldoi":"https://doi.org/10.1101/2024.03.01.582884","type":"preprint","status":"public","project":[{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","grant_number":"26137"},{"call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program","_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","grant_number":"101044865","_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6"},{"_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets"}],"ec_funded":1,"year":"2024","department":[{"_id":"GaNo"},{"_id":"JoDa"}],"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","researchdata_availability":"no"}]