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Various schemes for active sample stabilization have been demonstrated previously, with some reaching sub-nanometer stability in 3D. Here, we present a scheme for active drift correction that delivers the nanometer-scale 3D stability demanded by state-of-the-art super-resolution techniques and is straightforward to implement compared to previous schemes capable of reaching this level of stabilization precision. Using a refined algorithm that can handle various types of reference structure, without sparse signal peaks being mandatory, we stabilized sample position to ∼1 nm in 3D using objective lenses both with high and low numerical aperture. Our implementation requires only the addition of a simple widefield imaging path and we provide an open-source control software with graphical user interface to facilitate easy adoption of the module. Finally, we demonstrate how this has the potential to enhance data collection for diffraction-limited and super-resolution imaging techniques using single-molecule localization microscopy and cryo-confocal imaging as showcases.","lang":"eng"}],"issue":"2","oa_version":"Published Version","day":"11","author":[{"orcid":"0009-0000-7590-3501","id":"937696FA-C996-11E9-8C7C-CF13E6697425","first_name":"Jakob","last_name":"Vorlaufer","full_name":"Vorlaufer, Jakob"},{"id":"e64d39c7-72ef-11ef-b75a-ee3046860d1b","first_name":"Nikolai","last_name":"Semenov","full_name":"Semenov, Nikolai"},{"first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"id":"305ab18b-dc7d-11ea-9b2f-b58195228ea2","first_name":"Manjunath","last_name":"Javoor","full_name":"Javoor, Manjunath","orcid":"0000-0003-2311-2112"},{"full_name":"Zens, Bettina","last_name":"Zens","first_name":"Bettina","id":"45FD126C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9561-1239"},{"id":"40E7F008-F248-11E8-B48F-1D18A9856A87","first_name":"Nathalie","last_name":"Agudelo Duenas","full_name":"Agudelo Duenas, Nathalie"},{"orcid":"0000-0002-7667-6854","first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli"},{"last_name":"Suplata","full_name":"Suplata, Marek","id":"EE8452B8-C26A-11E9-B157-E80CE6697425","first_name":"Marek"},{"first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke","last_name":"Jahr","orcid":"0000-0003-0201-2315"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"id":"60aaa06c-3de5-11eb-9e53-baa88e955dcb","first_name":"Andreas","last_name":"Wartak","full_name":"Wartak, Andreas"},{"orcid":"0000-0003-4790-8078","first_name":"Florian Km","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian Km","last_name":"Schur"},{"full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"}],"DOAJ_listed":"1","article_type":"original","publication_status":"published","language":[{"iso":"eng"}],"type":"journal_article","title":"Image-based 3D active sample stabilization on the nanometer scale for optical microscopy","project":[{"name":"CryoMinflux-guided in-situ molecular census and structure determination","grant_number":"CZI01","_id":"62909c6f-2b32-11ec-9570-e1476aab5308"},{"name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","grant_number":"26137","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"},{"call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","grant_number":"W1232-B24"},{"grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}],"date_created":"2025-06-08T22:01:22Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2025","article_number":"100211","publication_identifier":{"eissn":["2667-0747"]},"acknowledgement":"We acknowledge expert support by ISTA’s scientific service units, including the Miba Machine Shop, the Electron Microscopy Facility, and the Lab Support Facility. This work has been made possible in part by CZI grant DAF2021-234754 and grant DOI: https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (funder DOI: https://doi.org/10.13039/100014989) (F.K.M.S. and J.G.D.). We further gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant DK W1232 (M.R.T. and J.G.D.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.L.); ISTA postdoctoral fellowship IST fellow (A.W.); and Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.).","doi":"10.1016/j.bpr.2025.100211","month":"06","OA_place":"publisher","publisher":"Elsevier","intvolume":"         5","citation":{"apa":"Vorlaufer, J., Semenov, N., Kreuzinger, C., Javoor, M., Zens, B., Agudelo Duenas, N., … Danzl, J. G. (2025). Image-based 3D active sample stabilization on the nanometer scale for optical microscopy. <i>Biophysical Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.bpr.2025.100211\">https://doi.org/10.1016/j.bpr.2025.100211</a>","mla":"Vorlaufer, Jakob, et al. “Image-Based 3D Active Sample Stabilization on the Nanometer Scale for Optical Microscopy.” <i>Biophysical Reports</i>, vol. 5, no. 2, 100211, Elsevier, 2025, doi:<a href=\"https://doi.org/10.1016/j.bpr.2025.100211\">10.1016/j.bpr.2025.100211</a>.","short":"J. Vorlaufer, N. Semenov, C. Kreuzinger, M. Javoor, B. Zens, N. Agudelo Duenas, M. Tavakoli, M. Suplata, W. Jahr, J. Lyudchik, A. Wartak, F.K. Schur, J.G. Danzl, Biophysical Reports 5 (2025).","ista":"Vorlaufer J, Semenov N, Kreuzinger C, Javoor M, Zens B, Agudelo Duenas N, Tavakoli M, Suplata M, Jahr W, Lyudchik J, Wartak A, Schur FK, Danzl JG. 2025. Image-based 3D active sample stabilization on the nanometer scale for optical microscopy. Biophysical Reports. 5(2), 100211.","ama":"Vorlaufer J, Semenov N, Kreuzinger C, et al. Image-based 3D active sample stabilization on the nanometer scale for optical microscopy. <i>Biophysical Reports</i>. 2025;5(2). doi:<a href=\"https://doi.org/10.1016/j.bpr.2025.100211\">10.1016/j.bpr.2025.100211</a>","chicago":"Vorlaufer, Jakob, Nikolai Semenov, Caroline Kreuzinger, Manjunath Javoor, Bettina Zens, Nathalie Agudelo Duenas, Mojtaba Tavakoli, et al. “Image-Based 3D Active Sample Stabilization on the Nanometer Scale for Optical Microscopy.” <i>Biophysical Reports</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.bpr.2025.100211\">https://doi.org/10.1016/j.bpr.2025.100211</a>.","ieee":"J. Vorlaufer <i>et al.</i>, “Image-based 3D active sample stabilization on the nanometer scale for optical microscopy,” <i>Biophysical Reports</i>, vol. 5, no. 2. Elsevier, 2025."},"has_accepted_license":"1","quality_controlled":"1","volume":5,"OA_type":"gold","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)"},"ec_funded":1,"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"EM-Fac"},{"_id":"LifeSc"}],"article_processing_charge":"Yes","_id":"19795","corr_author":"1","status":"public","file_date_updated":"2025-06-10T07:24:46Z","department":[{"_id":"JoDa"},{"_id":"GradSch"},{"_id":"FlSc"},{"_id":"EM-Fac"}],"ddc":["570"],"scopus_import":"1","oa":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"20206"}]},"date_updated":"2026-04-07T11:48:07Z"},{"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 labelling. 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."}],"date_published":"2025-03-03T00:00:00Z","file":[{"checksum":"d2c3efcd354f967290f91ff34dfb3cc1","relation":"main_file","access_level":"open_access","file_name":"Readme_Data_Tavakoli_et_al_2025.rtf","file_id":"19275","date_updated":"2025-02-28T16:50:39Z","creator":"jdanzl","file_size":1922,"success":1,"content_type":"text/rtf","date_created":"2025-02-28T16:50:39Z"},{"checksum":"b20cfb9b7030375f94d4b9bc5ce5cee9","file_id":"19089","file_name":"Fig1b 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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.","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>","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.","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.","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>."},"has_accepted_license":"1","OA_type":"hybrid","volume":642,"quality_controlled":"1","department":[{"_id":"JoDa"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"GaNo"}],"file_date_updated":"2025-07-03T06:55:20Z","ddc":["570"],"scopus_import":"1","corr_author":"1","_id":"19704","status":"public","date_updated":"2026-04-28T13:33:34Z","oa":1,"related_material":{"record":[{"status":"public","relation":"earlier_version","id":"18677"},{"id":"18697","status":"public","relation":"research_data"}],"link":[{"relation":"press_release","description":"News on ISTA website","url":"https://ista.ac.at/en/news/piecing-together-the-brain-puzzle/"}]},"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"}],"external_id":{"isi":["001483477000001"],"pmid":["40335689"]},"file":[{"checksum":"ebc99d7108e728f46db0a009292675ef","file_name":"2025_Nature_Tavakoli.pdf","file_id":"19959","relation":"main_file","access_level":"open_access","creator":"dernst","date_updated":"2025-07-03T06:55:20Z","success":1,"content_type":"application/pdf","date_created":"2025-07-03T06:55:20Z","file_size":133201290}],"date_published":"2025-06-12T00:00:00Z","publication":"Nature","day":"12","PlanS_conform":"1","author":[{"orcid":"0000-0002-7667-6854","first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"first_name":"Michał","last_name":"Januszewski","full_name":"Januszewski, Michał"},{"id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","first_name":"Vitali","last_name":"Vistunou","full_name":"Vistunou, Vitali"},{"first_name":"Nathalie","id":"40E7F008-F248-11E8-B48F-1D18A9856A87","full_name":"Agudelo Duenas, Nathalie","last_name":"Agudelo Duenas"},{"orcid":"0009-0000-7590-3501","full_name":"Vorlaufer, Jakob","last_name":"Vorlaufer","first_name":"Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105"},{"first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara","last_name":"Oliveira","full_name":"Oliveira, Bárbara"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"first_name":"Viren","last_name":"Jain","full_name":"Jain, Viren"},{"orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl"}],"oa_version":"Published Version","pmid":1,"language":[{"iso":"eng"}],"isi":1,"type":"journal_article","title":"Light-microscopy-based connectomic reconstruction of mammalian brain tissue","project":[{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","grant_number":"26137"},{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_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"},{"call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"}],"article_type":"original","publication_status":"published","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"year":"2025","doi":"10.1038/s41586-025-08985-1","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).","date_created":"2025-05-18T22:02:51Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd"},{"publication":"The Plant Cell","external_id":{"isi":["001462763100001"],"pmid":["39792900"]},"date_published":"2025-04-01T00:00:00Z","file":[{"relation":"main_file","access_level":"open_access","file_id":"20092","file_name":"2025_PlantCell_Gallei.pdf","checksum":"9d3f8218ff37a29f29c48a7bbe831bd3","file_size":53904111,"date_created":"2025-07-31T07:03:43Z","content_type":"application/pdf","success":1,"date_updated":"2025-07-31T07:03:43Z","creator":"dernst"}],"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"}],"oa_version":"Published Version","pmid":1,"issue":"4","author":[{"orcid":"0000-0003-1286-7368","full_name":"Gallei, Michelle C","last_name":"Gallei","first_name":"Michelle C","id":"35A03822-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Truckenbrodt, Sven M","last_name":"Truckenbrodt","first_name":"Sven M","id":"45812BD4-F248-11E8-B48F-1D18A9856A87"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline"},{"first_name":"Syamala","id":"F8660870-D756-11E9-98C5-34DFE5697425","full_name":"Inumella, Syamala","last_name":"Inumella","orcid":"0009-0002-5890-120X"},{"full_name":"Vistunou, Vitali","last_name":"Vistunou","first_name":"Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81"},{"orcid":"0000-0003-1216-9105","last_name":"Sommer","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba","last_name":"Tavakoli","full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854"},{"full_name":"Agudelo Duenas, Nathalie","last_name":"Agudelo Duenas","first_name":"Nathalie","id":"40E7F008-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Vorlaufer","full_name":"Vorlaufer, Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425","first_name":"Jakob","orcid":"0009-0000-7590-3501"},{"orcid":"0000-0003-0201-2315","first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke","last_name":"Jahr"},{"full_name":"Randuch, Marek","last_name":"Randuch","first_name":"Marek","id":"6ac4636d-15b2-11ec-abd3-fb8df79972ae"},{"last_name":"Johnson","full_name":"Johnson, Alexander J","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander J","orcid":"0000-0002-2739-8843"},{"first_name":"Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","full_name":"Benková, Eva","last_name":"Benková","orcid":"0000-0002-8510-9739"},{"orcid":"0000-0002-8302-7596","first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","full_name":"Friml, Jiří","last_name":"Friml"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G"}],"PlanS_conform":"1","day":"01","publication_status":"published","article_type":"original","title":"Super-resolution expansion microscopy in plant roots","type":"journal_article","project":[{"call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425"},{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"_id":"269B5B22-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 679-2018","name":"UltraX - achieving sub-nanometer resolution in light microscopy using iterative X10 microscopy in combination with nanobodies and STED"},{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","grant_number":"26137"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"}],"isi":1,"language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2025-02-05T06:52:06Z","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.","doi":"10.1093/plcell/koaf006","year":"2025","publication_identifier":{"eissn":["1532-298X"],"issn":["1040-4651"]},"article_number":"koaf006","month":"04","OA_place":"publisher","intvolume":"        37","publisher":"Oxford University Press","quality_controlled":"1","volume":37,"OA_type":"hybrid","citation":{"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>","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.","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>","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>.","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."},"has_accepted_license":"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)"},"ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"},{"_id":"M-Shop"}],"article_processing_charge":"Yes (via OA deal)","status":"public","_id":"19003","corr_author":"1","scopus_import":"1","file_date_updated":"2025-07-31T07:03:43Z","department":[{"_id":"EvBe"},{"_id":"JoDa"},{"_id":"JiFr"}],"ddc":["580"],"related_material":{"record":[{"relation":"earlier_version","status":"public","id":"18689"},{"id":"18837","relation":"research_data","status":"public"}]},"oa":1,"date_updated":"2026-06-10T08:30:19Z"},{"month":"04","file":[{"relation":"main_file","access_level":"open_access","file_name":"Fig 1D+2D 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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."}],"publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","has_accepted_license":"1","citation":{"short":"J.G. Danzl, C. Kreuzinger, (2025).","ista":"Danzl JG, Kreuzinger C. 2025. Research Data for the publication ‘Super-resolution expansion microscopy in plant roots’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18837\">10.15479/AT:ISTA:18837</a>.","apa":"Danzl, J. G., &#38; Kreuzinger, C. (2025). Research Data for the publication “Super-resolution expansion microscopy in plant roots.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18837\">https://doi.org/10.15479/AT:ISTA:18837</a>","mla":"Danzl, Johann G., and Caroline Kreuzinger. <i>Research Data for the Publication “Super-Resolution Expansion Microscopy in Plant Roots.”</i> Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18837\">10.15479/AT:ISTA:18837</a>.","ieee":"J. G. Danzl and C. Kreuzinger, “Research Data for the publication ‘Super-resolution expansion microscopy in plant roots.’” Institute of Science and Technology Austria, 2025.","chicago":"Danzl, Johann G, and Caroline Kreuzinger. “Research Data for the Publication ‘Super-Resolution Expansion Microscopy in Plant Roots.’” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:18837\">https://doi.org/10.15479/AT:ISTA:18837</a>.","ama":"Danzl JG, Kreuzinger C. Research Data for the publication “Super-resolution expansion microscopy in plant roots.” 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18837\">10.15479/AT:ISTA:18837</a>"},"author":[{"orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"},{"last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"}],"article_processing_charge":"No","tmp":{"image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","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"},"status":"public","contributor":[{"orcid":"0000-0003-1286-7368","contributor_type":"researcher","id":"35A03822-F248-11E8-B48F-1D18A9856A87","first_name":"Michelle C","last_name":"Gallei"},{"last_name":"Truckenbrodt","contributor_type":"researcher","id":"45812BD4-F248-11E8-B48F-1D18A9856A87","first_name":"Sven M"},{"first_name":"Caroline","contributor_type":"researcher","id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger"},{"first_name":"Syamala","contributor_type":"researcher","id":"F8660870-D756-11E9-98C5-34DFE5697425","last_name":"Inumella"},{"contributor_type":"researcher","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","first_name":"Vitali","last_name":"Vistunou"},{"first_name":"Christoph M","contributor_type":"researcher","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","orcid":"0000-0003-1216-9105"},{"first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","last_name":"Tavakoli","orcid":"0000-0002-7667-6854"},{"last_name":"Agudelo Duenas","contributor_type":"researcher","id":"40E7F008-F248-11E8-B48F-1D18A9856A87","first_name":"Nathalie"},{"first_name":"Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425","contributor_type":"researcher","last_name":"Vorlaufer"},{"contributor_type":"researcher","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","last_name":"Jahr"},{"id":"6ac4636d-15b2-11ec-abd3-fb8df79972ae","contributor_type":"researcher","first_name":"Marek","last_name":"Randuch"},{"orcid":"0000-0002-2739-8843","last_name":"Johnson","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","first_name":"Alexander J"},{"first_name":"Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","last_name":"Benková","orcid":"0000-0002-8510-9739"},{"orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","first_name":"Jiří","last_name":"Friml"},{"last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","first_name":"Johann G","orcid":"0000-0001-8559-3973"}],"corr_author":"1","_id":"18837","title":"Research Data for the publication \"Super-resolution expansion microscopy in plant roots\"","type":"research_data","file_date_updated":"2025-03-07T11:09:13Z","department":[{"_id":"JoDa"}],"user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","oa":1,"date_created":"2025-01-13T09:51:29Z","related_material":{"record":[{"id":"19003","relation":"used_in_publication","status":"public"}]},"date_updated":"2026-06-10T08:30:20Z","doi":"10.15479/AT:ISTA:18837","year":"2025"},{"publication_status":"draft","type":"preprint","title":"Super-resolution expansion microscopy in plant roots","project":[{"call_identifier":"H2020","_id":"261099A6-B435-11E9-9278-68D0E5697425","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","grant_number":"742985"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"ALTF 679-2018","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"}],"language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2024-12-19T12:28:00Z","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.","doi":"10.1101/2024.02.21.581330","year":"2024","publication":"bioRxiv","date_published":"2024-02-21T00:00:00Z","abstract":[{"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.","lang":"eng"}],"oa_version":"Preprint","main_file_link":[{"url":"https://doi.org/10.1101/2024.02.21.581330","open_access":"1"}],"author":[{"orcid":"0000-0003-1286-7368","full_name":"Gallei, Michelle C","last_name":"Gallei","first_name":"Michelle C","id":"35A03822-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Truckenbrodt, Sven M","last_name":"Truckenbrodt","first_name":"Sven M","id":"45812BD4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger","first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0009-0002-5890-120X","first_name":"Syamala","id":"F8660870-D756-11E9-98C5-34DFE5697425","full_name":"Inumella, Syamala","last_name":"Inumella"},{"first_name":"Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","full_name":"Vistunou, Vitali","last_name":"Vistunou"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105"},{"orcid":"0000-0002-7667-6854","first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli"},{"id":"40E7F008-F248-11E8-B48F-1D18A9856A87","first_name":"Nathalie","last_name":"Agudelo Duenas","full_name":"Agudelo Duenas, Nathalie"},{"first_name":"Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425","full_name":"Vorlaufer, Jakob","last_name":"Vorlaufer","orcid":"0009-0000-7590-3501"},{"last_name":"Jahr","full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","orcid":"0000-0003-0201-2315"},{"id":"6ac4636d-15b2-11ec-abd3-fb8df79972ae","first_name":"Marek","last_name":"Randuch","full_name":"Randuch, Marek"},{"orcid":"0000-0002-2739-8843","first_name":"Alexander J","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","full_name":"Johnson, Alexander J","last_name":"Johnson"},{"first_name":"Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","full_name":"Benková, Eva","last_name":"Benková","orcid":"0000-0002-8510-9739"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","last_name":"Friml","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596"},{"orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"day":"21","status":"public","_id":"18689","corr_author":"1","department":[{"_id":"EvBe"},{"_id":"JoDa"},{"_id":"JiFr"}],"oa":1,"related_material":{"record":[{"id":"19003","status":"public","relation":"later_version"},{"id":"18681","relation":"dissertation_contains","status":"public"}]},"date_updated":"2026-04-07T12:56:36Z","month":"02","OA_place":"repository","citation":{"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>.","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.).","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>","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>.","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>","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>."},"tmp":{"image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","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"},"article_processing_charge":"No","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"ec_funded":1},{"month":"07","OA_place":"repository","tmp":{"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","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"ec_funded":1,"article_processing_charge":"No","acknowledged_ssus":[{"_id":"E-Lib"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"ScienComp"}],"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.).","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>.","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>.","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>.","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>"},"department":[{"_id":"GaNo"},{"_id":"JoDa"}],"status":"public","_id":"18677","corr_author":"1","date_updated":"2026-04-28T13:33:34Z","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"18681"},{"status":"public","relation":"dissertation_contains","id":"18674"},{"id":"19704","relation":"later_version","status":"public"}]},"oa":1,"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 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.","lang":"eng"}],"publication":"bioRxiv","date_published":"2024-07-08T00:00:00Z","author":[{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba","last_name":"Tavakoli","full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"first_name":"Michał","last_name":"Januszewski","full_name":"Januszewski, Michał"},{"last_name":"Vistunou","full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","first_name":"Vitali"},{"full_name":"Agudelo Duenas, Nathalie","last_name":"Agudelo Duenas","first_name":"Nathalie","id":"40E7F008-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425","full_name":"Vorlaufer, Jakob","last_name":"Vorlaufer","orcid":"0009-0000-7590-3501"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"},{"last_name":"Oliveira","full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178"},{"full_name":"Jain, Viren","last_name":"Jain","first_name":"Viren"},{"last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","orcid":"0000-0001-8559-3973"}],"day":"08","oa_version":"Preprint","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2024.03.01.582884"}],"title":"Light-microscopy based dense connectomic reconstruction of mammalian brain tissue","type":"preprint","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","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"},{"_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"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"}],"language":[{"iso":"eng"}],"publication_status":"draft","doi":"10.1101/2024.03.01.582884","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","year":"2024","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2024-12-18T14:48:24Z"},{"pmid":1,"oa_version":"Published Version","author":[{"first_name":"Jacek","full_name":"Glajzer, Jacek","last_name":"Glajzer"},{"full_name":"Castillo-Tong, Dan Cacsire","last_name":"Castillo-Tong","first_name":"Dan Cacsire"},{"first_name":"Rolf","last_name":"Richter","full_name":"Richter, Rolf"},{"last_name":"Vergote","full_name":"Vergote, Ignace","first_name":"Ignace"},{"first_name":"Hagen","last_name":"Kulbe","full_name":"Kulbe, Hagen"},{"first_name":"Adriaan","full_name":"Vanderstichele, Adriaan","last_name":"Vanderstichele"},{"first_name":"Ilary","full_name":"Ruscito, Ilary","last_name":"Ruscito"},{"first_name":"Fabian","full_name":"Trillsch, Fabian","last_name":"Trillsch"},{"full_name":"Mustea, Alexander","last_name":"Mustea","first_name":"Alexander"},{"last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"},{"full_name":"Gourley, Charlie","last_name":"Gourley","first_name":"Charlie"},{"full_name":"Gabra, Hani","last_name":"Gabra","first_name":"Hani"},{"first_name":"Eliane T.","full_name":"Taube, Eliane T.","last_name":"Taube"},{"last_name":"Dorigo","full_name":"Dorigo, Oliver","first_name":"Oliver"},{"first_name":"David","last_name":"Horst","full_name":"Horst, David"},{"last_name":"Keunecke","full_name":"Keunecke, Carlotta","first_name":"Carlotta"},{"last_name":"Baum","full_name":"Baum, Joanna","first_name":"Joanna"},{"first_name":"Timothy","last_name":"Angelotti","full_name":"Angelotti, Timothy"},{"first_name":"Jalid","last_name":"Sehouli","full_name":"Sehouli, Jalid"},{"first_name":"Elena Ioana","full_name":"Braicu, Elena Ioana","last_name":"Braicu"}],"day":"01","publication":"Annals of Surgical Oncology","file":[{"file_id":"12490","file_name":"2023_AnnalsSurgicalOncology_Glajzer.pdf","relation":"main_file","access_level":"open_access","checksum":"36a1200e1011f4b2155a8041d0308f34","content_type":"application/pdf","date_created":"2023-02-02T13:01:20Z","success":1,"file_size":365865,"creator":"dernst","date_updated":"2023-02-02T13:01:20Z"}],"external_id":{"pmid":["36085390"],"isi":["000852125500006"]},"date_published":"2023-01-01T00:00:00Z","abstract":[{"text":"Background: This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC).\r\n\r\nPatients and Methods: Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups.\r\n\r\nResults: Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence.\r\n\r\nConclusions: Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2023-01-16T09:44:36Z","keyword":["Oncology","Surgery"],"doi":"10.1245/s10434-022-12459-3","acknowledgement":"E.I.B. is a Feodor Lynen fellow of the Humboldt Foundation and a participant of the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health. This work was supported by European Commission’s Seventh Framework Programme under grant agreement no. 279113 (OCTIPS; www.octips.eu).\r\nOpen Access funding enabled and organized by Projekt DEAL.","publication_identifier":{"issn":["1068-9265"],"eissn":["1534-4681"]},"year":"2023","publication_status":"published","article_type":"original","title":"Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium","type":"journal_article","language":[{"iso":"eng"}],"isi":1,"quality_controlled":"1","volume":30,"has_accepted_license":"1","citation":{"short":"J. Glajzer, D.C. Castillo-Tong, R. Richter, I. Vergote, H. Kulbe, A. Vanderstichele, I. Ruscito, F. Trillsch, A. Mustea, C. Kreuzinger, C. Gourley, H. Gabra, E.T. Taube, O. Dorigo, D. Horst, C. Keunecke, J. Baum, T. Angelotti, J. Sehouli, E.I. Braicu, Annals of Surgical Oncology 30 (2023) 35–45.","ista":"Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET, Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI. 2023. Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. Annals of Surgical Oncology. 30, 35–45.","mla":"Glajzer, Jacek, et al. “Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>, vol. 30, Springer Nature, 2023, pp. 35–45, doi:<a href=\"https://doi.org/10.1245/s10434-022-12459-3\">10.1245/s10434-022-12459-3</a>.","apa":"Glajzer, J., Castillo-Tong, D. C., Richter, R., Vergote, I., Kulbe, H., Vanderstichele, A., … Braicu, E. I. (2023). Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. Springer Nature. <a href=\"https://doi.org/10.1245/s10434-022-12459-3\">https://doi.org/10.1245/s10434-022-12459-3</a>","ieee":"J. Glajzer <i>et al.</i>, “Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium,” <i>Annals of Surgical Oncology</i>, vol. 30. Springer Nature, pp. 35–45, 2023.","chicago":"Glajzer, Jacek, Dan Cacsire Castillo-Tong, Rolf Richter, Ignace Vergote, Hagen Kulbe, Adriaan Vanderstichele, Ilary Ruscito, et al. “Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1245/s10434-022-12459-3\">https://doi.org/10.1245/s10434-022-12459-3</a>.","ama":"Glajzer J, Castillo-Tong DC, Richter R, et al. Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. 2023;30:35-45. doi:<a href=\"https://doi.org/10.1245/s10434-022-12459-3\">10.1245/s10434-022-12459-3</a>"},"page":"35-45","article_processing_charge":"No","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)"},"month":"01","intvolume":"        30","publisher":"Springer Nature","related_material":{"record":[{"id":"12115","status":"public","relation":"other"}]},"oa":1,"date_updated":"2026-06-18T17:21:24Z","status":"public","_id":"12205","scopus_import":"1","ddc":["610"],"department":[{"_id":"JoDa"}],"file_date_updated":"2023-02-02T13:01:20Z"},{"publication_status":"published","article_type":"original","type":"journal_article","title":"ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium","isi":1,"language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2023-01-12T11:56:22Z","keyword":["Oncology","Surgery"],"acknowledgement":"This work was supported by European Commission’s Seventh Framework Programme under Grant Agreement No. 279113 (OCTIPS; www.octips.eu).","doi":"10.1245/s10434-022-12681-z","year":"2023","publication_identifier":{"issn":["1068-9265"],"eissn":["1534-4681"]},"publication":"Annals of Surgical Oncology","external_id":{"isi":["000879151800001"]},"date_published":"2023-01-01T00:00:00Z","oa_version":"Published Version","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1245/s10434-022-12681-z"}],"author":[{"first_name":"Jacek","full_name":"Glajzer, Jacek","last_name":"Glajzer"},{"first_name":"Dan Cacsire","full_name":"Castillo-Tong, Dan Cacsire","last_name":"Castillo-Tong"},{"full_name":"Richter, Rolf","last_name":"Richter","first_name":"Rolf"},{"first_name":"Ignace","full_name":"Vergote, Ignace","last_name":"Vergote"},{"first_name":"Hagen","last_name":"Kulbe","full_name":"Kulbe, Hagen"},{"first_name":"Adriaan","full_name":"Vanderstichele, Adriaan","last_name":"Vanderstichele"},{"first_name":"Ilary","full_name":"Ruscito, Ilary","last_name":"Ruscito"},{"first_name":"Fabian","full_name":"Trillsch, Fabian","last_name":"Trillsch"},{"full_name":"Mustea, Alexander","last_name":"Mustea","first_name":"Alexander"},{"first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"first_name":"Charlie","last_name":"Gourley","full_name":"Gourley, Charlie"},{"full_name":"Gabra, Hani","last_name":"Gabra","first_name":"Hani"},{"last_name":"Taube","full_name":"Taube, Eliane T.","first_name":"Eliane T."},{"first_name":"Oliver","full_name":"Dorigo, Oliver","last_name":"Dorigo"},{"first_name":"David","last_name":"Horst","full_name":"Horst, David"},{"first_name":"Carlotta","full_name":"Keunecke, Carlotta","last_name":"Keunecke"},{"first_name":"Joanna","full_name":"Baum, Joanna","last_name":"Baum"},{"first_name":"Timothy","last_name":"Angelotti","full_name":"Angelotti, Timothy"},{"first_name":"Jalid","full_name":"Sehouli, Jalid","last_name":"Sehouli"},{"full_name":"Braicu, Elena Ioana","last_name":"Braicu","first_name":"Elena Ioana"}],"day":"01","status":"public","_id":"12115","scopus_import":"1","ddc":["570"],"department":[{"_id":"JoDa"}],"oa":1,"related_material":{"record":[{"id":"12205","relation":"other","status":"public"}]},"date_updated":"2026-06-18T17:21:25Z","month":"01","intvolume":"        30","publisher":"Springer Nature","quality_controlled":"1","volume":30,"citation":{"mla":"Glajzer, Jacek, et al. “ASO Visual Abstract: Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome, and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer (HGSOC). A Multicenter, Retrospective Study of the Ovarian Cancer Therapy—Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>, vol. 30, Springer Nature, 2023, pp. 46–47, doi:<a href=\"https://doi.org/10.1245/s10434-022-12681-z\">10.1245/s10434-022-12681-z</a>.","apa":"Glajzer, J., Castillo-Tong, D. C., Richter, R., Vergote, I., Kulbe, H., Vanderstichele, A., … Braicu, E. I. (2023). ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. Springer Nature. <a href=\"https://doi.org/10.1245/s10434-022-12681-z\">https://doi.org/10.1245/s10434-022-12681-z</a>","ista":"Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET, Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI. 2023. ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium. Annals of Surgical Oncology. 30, 46–47.","short":"J. Glajzer, D.C. Castillo-Tong, R. Richter, I. Vergote, H. Kulbe, A. Vanderstichele, I. Ruscito, F. Trillsch, A. Mustea, C. Kreuzinger, C. Gourley, H. Gabra, E.T. Taube, O. Dorigo, D. Horst, C. Keunecke, J. Baum, T. Angelotti, J. Sehouli, E.I. Braicu, Annals of Surgical Oncology 30 (2023) 46–47.","ama":"Glajzer J, Castillo-Tong DC, Richter R, et al. ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. 2023;30:46-47. doi:<a href=\"https://doi.org/10.1245/s10434-022-12681-z\">10.1245/s10434-022-12681-z</a>","chicago":"Glajzer, Jacek, Dan Cacsire Castillo-Tong, Rolf Richter, Ignace Vergote, Hagen Kulbe, Adriaan Vanderstichele, Ilary Ruscito, et al. “ASO Visual Abstract: Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome, and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer (HGSOC). A Multicenter, Retrospective Study of the Ovarian Cancer Therapy—Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1245/s10434-022-12681-z\">https://doi.org/10.1245/s10434-022-12681-z</a>.","ieee":"J. Glajzer <i>et al.</i>, “ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium,” <i>Annals of Surgical Oncology</i>, vol. 30. Springer Nature, pp. 46–47, 2023."},"page":"46-47","article_processing_charge":"No"},{"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"}],"file":[{"file_size":9358599,"success":1,"content_type":"application/pdf","date_created":"2021-05-28T12:39:43Z","date_updated":"2021-05-28T12:39:43Z","creator":"kschuh","relation":"main_file","access_level":"open_access","file_name":"2021_NatureCommunications_Morandell.pdf","file_id":"9430","checksum":"337e0f7959c35ec959984cacdcb472ba"}],"external_id":{"isi":["000658769900010"]},"date_published":"2021-05-24T00:00:00Z","publication":"Nature Communications","day":"24","author":[{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"last_name":"Schwarz","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A"},{"orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","last_name":"Basilico","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","last_name":"Tasciyan","full_name":"Tasciyan, Saren"},{"orcid":"0000-0001-8370-6161","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","first_name":"Georgi A","last_name":"Dimchev","full_name":"Dimchev, Georgi A"},{"full_name":"Nicolas, Armel","last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1216-9105","last_name":"Sommer","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"full_name":"Dotter, Christoph","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096"},{"first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","last_name":"Knaus"},{"first_name":"Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","last_name":"Dobler"},{"last_name":"Cacci","full_name":"Cacci, Emanuele","first_name":"Emanuele"},{"orcid":"0000-0003-4790-8078","full_name":"Schur, Florian KM","last_name":"Schur","first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"issue":"1","oa_version":"Published Version","language":[{"iso":"eng"}],"isi":1,"type":"journal_article","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","call_identifier":"H2020"},{"call_identifier":"FWF","grant_number":"W1232","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"grant_number":"F7807","name":"Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"}],"article_type":"original","publication_status":"published","year":"2021","article_number":"3058","publication_identifier":{"eissn":["2041-1723"]},"doi":"10.1038/s41467-021-23123-x","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).","keyword":["General Biochemistry","Genetics and Molecular Biology"],"date_created":"2021-05-28T11:49:46Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","intvolume":"        12","month":"05","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)"},"ec_funded":1,"acknowledged_ssus":[{"_id":"PreCl"}],"article_processing_charge":"No","citation":{"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>","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>.","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).","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.","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>."},"has_accepted_license":"1","quality_controlled":"1","volume":12,"file_date_updated":"2021-05-28T12:39:43Z","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"ddc":["572"],"scopus_import":"1","corr_author":"1","_id":"9429","status":"public","date_updated":"2026-06-21T22:31:15Z","related_material":{"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}],"record":[{"id":"19557","status":"public","relation":"dissertation_contains"},{"relation":"earlier_version","status":"public","id":"7800"},{"status":"public","relation":"dissertation_contains","id":"12401"}]},"oa":1},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2020-05-05T14:31:33Z","doi":"10.1101/2020.01.10.902064 ","year":"2020","publication_status":"draft","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","type":"preprint","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF"},{"name":"Molecular Drug Targets","grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"language":[{"iso":"eng"}],"oa_version":"Preprint","author":[{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A","last_name":"Schwarz","full_name":"Schwarz, Lena A"},{"orcid":"0000-0003-1843-3173","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","full_name":"Basilico, Bernadette","last_name":"Basilico"},{"last_name":"Tasciyan","full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","orcid":"0000-0003-1671-393X"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","last_name":"Nicolas","full_name":"Nicolas, Armel"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105"},{"last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"},{"first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","last_name":"Knaus"},{"full_name":"Dobler, Zoe","last_name":"Dobler","first_name":"Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F"},{"first_name":"Emanuele","last_name":"Cacci","full_name":"Cacci, Emanuele"},{"full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"day":"11","publication":"bioRxiv","date_published":"2020-01-11T00:00:00Z","file":[{"checksum":"c6799ab5daba80efe8e2ed63c15f8c81","file_name":"2020.01.10.902064v1.full.pdf","file_id":"7801","access_level":"open_access","relation":"main_file","creator":"rsix","date_updated":"2020-07-14T12:48:03Z","content_type":"application/pdf","date_created":"2020-05-05T14:31:19Z","file_size":2931370}],"abstract":[{"lang":"eng","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."}],"oa":1,"related_material":{"record":[{"status":"public","relation":"later_version","id":"9429"},{"status":"public","relation":"dissertation_contains","id":"8620"}]},"date_updated":"2026-06-21T22:31:11Z","status":"public","corr_author":"1","_id":"7800","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"file_date_updated":"2020-07-14T12:48:03Z","ddc":["570"],"citation":{"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>.","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.).","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>. Cold Spring Harbor Laboratory. <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>, Cold Spring Harbor Laboratory, 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>. Cold Spring Harbor Laboratory.","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>","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>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>."},"has_accepted_license":"1","tmp":{"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","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"article_processing_charge":"No","acknowledged_ssus":[{"_id":"PreCl"}],"month":"01","publisher":"Cold Spring Harbor Laboratory"}]