[{"oa_version":"Published Version","article_processing_charge":"Yes","file_date_updated":"2025-07-07T09:52:46Z","date_published":"2025-07-01T00:00:00Z","year":"2025","language":[{"iso":"eng"}],"oa":1,"tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"scopus_import":"1","_id":"8616","citation":{"ista":"Gao X, Li J-L, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J-M, Yi Y, Zhang S, Shi Y-C, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco DB, Lu Y, Yang S, Adams RH, Lindner V, Huang F, Wu L-J, Zheng H, Han F, Hippenmeyer S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Körbelin J, Trepel M, Lu H, Zhou BO, Zhao H, Su W, Bachoo RM, Ge W. 2025. Reduction of neuronal activity mediated by blood-vessel regression in the brain. Nature Communications. 16, 5840.","apa":"Gao, X., Li, J.-L., Chen, X., Ci, B., Chen, F., Lu, N., … Ge, W. (2025). Reduction of neuronal activity mediated by blood-vessel regression in the brain. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-025-60308-0\">https://doi.org/10.1038/s41467-025-60308-0</a>","ama":"Gao X, Li J-L, Chen X, et al. Reduction of neuronal activity mediated by blood-vessel regression in the brain. <i>Nature Communications</i>. 2025;16. doi:<a href=\"https://doi.org/10.1038/s41467-025-60308-0\">10.1038/s41467-025-60308-0</a>","mla":"Gao, Xiaofei, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” <i>Nature Communications</i>, vol. 16, 5840, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41467-025-60308-0\">10.1038/s41467-025-60308-0</a>.","ieee":"X. Gao <i>et al.</i>, “Reduction of neuronal activity mediated by blood-vessel regression in the brain,” <i>Nature Communications</i>, vol. 16. Springer Nature, 2025.","chicago":"Gao, Xiaofei, Jun-Liszt Li, Xingjun Chen, Bo Ci, Fei Chen, Nannan Lu, Bo Shen, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” <i>Nature Communications</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41467-025-60308-0\">https://doi.org/10.1038/s41467-025-60308-0</a>.","short":"X. Gao, J.-L. Li, X. Chen, B. Ci, F. Chen, N. Lu, B. Shen, L. Zheng, J.-M. Jia, Y. Yi, S. Zhang, Y.-C. Shi, K. Shi, N.E. Propson, Y. Huang, K. Poinsatte, Z. Zhang, Y. Yue, D.B. Bosco, Y. Lu, S. Yang, R.H. Adams, V. Lindner, F. Huang, L.-J. Wu, H. Zheng, F. Han, S. Hippenmeyer, A.M. Stowe, B. Peng, M. Margeta, X. Wang, Q. Liu, J. Körbelin, M. Trepel, H. Lu, B.O. Zhou, H. Zhao, W. Su, R.M. Bachoo, W. Ge, Nature Communications 16 (2025)."},"quality_controlled":"1","status":"public","ec_funded":1,"article_number":"5840","has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"01","publication":"Nature Communications","article_type":"original","publication_status":"published","isi":1,"OA_place":"publisher","external_id":{"isi":["001523450500035"]},"publisher":"Springer Nature","OA_type":"gold","author":[{"first_name":"Xiaofei","full_name":"Gao, Xiaofei","last_name":"Gao"},{"full_name":"Li, Jun-Liszt","first_name":"Jun-Liszt","last_name":"Li"},{"last_name":"Chen","full_name":"Chen, Xingjun","first_name":"Xingjun"},{"full_name":"Ci, Bo","first_name":"Bo","last_name":"Ci"},{"first_name":"Fei","full_name":"Chen, Fei","last_name":"Chen"},{"last_name":"Lu","first_name":"Nannan","full_name":"Lu, Nannan"},{"last_name":"Shen","full_name":"Shen, Bo","first_name":"Bo"},{"last_name":"Zheng","first_name":"Lijun","full_name":"Zheng, Lijun"},{"last_name":"Jia","first_name":"Jie-Min","full_name":"Jia, Jie-Min"},{"last_name":"Yi","first_name":"Yating","full_name":"Yi, Yating"},{"first_name":"Shiwen","full_name":"Zhang, Shiwen","last_name":"Zhang"},{"last_name":"Shi","first_name":"Ying-Chao","full_name":"Shi, Ying-Chao"},{"last_name":"Shi","full_name":"Shi, Kaibin","first_name":"Kaibin"},{"first_name":"Nicholas E","full_name":"Propson, Nicholas E","last_name":"Propson"},{"last_name":"Huang","first_name":"Yubin","full_name":"Huang, Yubin"},{"first_name":"Katherine","full_name":"Poinsatte, Katherine","last_name":"Poinsatte"},{"full_name":"Zhang, Zhaohuan","first_name":"Zhaohuan","last_name":"Zhang"},{"first_name":"Yuanlei","full_name":"Yue, Yuanlei","last_name":"Yue"},{"last_name":"Bosco","full_name":"Bosco, Dale B","first_name":"Dale B"},{"last_name":"Lu","first_name":"Ying-mei","full_name":"Lu, Ying-mei"},{"full_name":"Yang, Shi-bing","first_name":"Shi-bing","last_name":"Yang"},{"full_name":"Adams, Ralf H.","first_name":"Ralf H.","last_name":"Adams"},{"last_name":"Lindner","full_name":"Lindner, Volkhard","first_name":"Volkhard"},{"last_name":"Huang","full_name":"Huang, Fen","first_name":"Fen"},{"last_name":"Wu","full_name":"Wu, Long-Jun","first_name":"Long-Jun"},{"last_name":"Zheng","first_name":"Hui","full_name":"Zheng, Hui"},{"full_name":"Han, Feng","first_name":"Feng","last_name":"Han"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"},{"last_name":"Stowe","first_name":"Ann M.","full_name":"Stowe, Ann M."},{"last_name":"Peng","first_name":"Bo","full_name":"Peng, Bo"},{"last_name":"Margeta","full_name":"Margeta, Marta","first_name":"Marta"},{"first_name":"Xiaoqun","full_name":"Wang, Xiaoqun","last_name":"Wang"},{"last_name":"Liu","first_name":"Qiang","full_name":"Liu, Qiang"},{"last_name":"Körbelin","first_name":"Jakob","full_name":"Körbelin, Jakob"},{"first_name":"Martin","full_name":"Trepel, Martin","last_name":"Trepel"},{"first_name":"Hui","full_name":"Lu, Hui","last_name":"Lu"},{"full_name":"Zhou, Bo O.","first_name":"Bo O.","last_name":"Zhou"},{"full_name":"Zhao, Hu","first_name":"Hu","last_name":"Zhao"},{"first_name":"Wenzhi","full_name":"Su, Wenzhi","last_name":"Su"},{"last_name":"Bachoo","full_name":"Bachoo, Robert M.","first_name":"Robert M."},{"last_name":"Ge","first_name":"Woo-ping","full_name":"Ge, Woo-ping"}],"date_created":"2020-10-06T08:58:59Z","intvolume":"        16","department":[{"_id":"SiHi"}],"date_updated":"2025-09-04T07:08:37Z","doi":"10.1038/s41467-025-60308-0","acknowledgement":"The project was initiated in the Jan lab at UCSF. We thank Lily Jan and Yuh-Nung Jan’s generous support. We thank Liqun Luo’s lab for providing MADM-7 mice and Rolf A Brekken for VEGF-antibodies.  Drs. Yuanquan Song (UPenn), Zhaozhu Hu (JHU), Ji Hu (ShanghaiTech), Yang Xiang (U. Mass), Hao Wang (Zhejiang U.) and Ruikang Wang (U. Washington) for critical input, colleagues at Children’s Research Institute, Departments of Neuroscience, Neurology and Neurotherapeutics, Pediatrics from UT Southwestern, and colleagues from the Jan lab for discussion. Dr. Bridget Samuels, Sean Morrison (UT Southwestern), and Nannan Lu (Zhejiang U.) for critical reading. We acknowledge the assistance of the CIBR Imaging core. We also thank UT Southwestern Live Cell Imaging Facility, a Shared Resource of the Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support Grant, P30 CA142543K. This work is supported by CIBR funds and the American Heart Association AWRP Summer 2016 Innovative Research Grant (17IRG33410377) to W-P.G.; National Natural Science Foundation of China (No.81370031) to Z.Z.;National Key Research and Development Program of China (2016YFE0125400)to F.H.;National Natural Science Foundations of China (No. 81473202) to Y.L.; National Natural Science Foundation of China (No.31600839) and Shenzhen Science and Technology Research Program (JCYJ20170818163320865) to B.P.; National Natural Science Foundation of China (No. 31800864) and Westlake University start-up funds to J-M. J. NIH R01NS088627 to W.L.J.; NIH: R01 AG020670 and RF1AG054111 to H.Z.; R01 NS088555 to A.M.S., and European Research Council No.725780 to S.H.;W-P.G. was a recipient of Bugher-American Heart Association Dan Adams Thinking Outside the Box Award.","abstract":[{"text":"The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain.","lang":"eng"}],"volume":16,"fulldoi":"https://doi.org/10.1038/s41467-025-60308-0","type":"journal_article","file":[{"file_size":17018106,"file_id":"19971","checksum":"f59748cb67232cfb210035d9aef60836","creator":"dernst","file_name":"2025_NatureComm_Gao.pdf","relation":"main_file","access_level":"open_access","content_type":"application/pdf","date_updated":"2025-07-07T09:52:46Z","success":1,"date_created":"2025-07-07T09:52:46Z"}],"project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"DOAJ_listed":"1","ddc":["570"],"month":"07","title":"Reduction of neuronal activity mediated by blood-vessel regression in the brain","publication_identifier":{"eissn":["2041-1723"]}},{"OA_place":"repository","publication_status":"submitted","external_id":{"biorxivid":["10.1101/2025.05.22.655488"]},"OA_type":"green","date_created":"2025-05-29T10:45:55Z","author":[{"first_name":"Adrián","full_name":"Cárdenas, Adrián","last_name":"Cárdenas"},{"first_name":"Irem","full_name":"Çelik, Irem","last_name":"Çelik"},{"last_name":"Espinós","full_name":"Espinós, Alexandre","first_name":"Alexandre"},{"last_name":"Streicher","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"last_name":"López-González","full_name":"López-González, Lara","first_name":"Lara"},{"last_name":"del-Valle-Anton","full_name":"del-Valle-Anton, Lucia","first_name":"Lucia"},{"first_name":"Virginia","full_name":"Fernández, Virginia","last_name":"Fernández"},{"last_name":"Amin","full_name":"Amin, Salma","first_name":"Salma"},{"first_name":"Enrico","full_name":"Negri, Enrico","last_name":"Negri"},{"full_name":"Ortuño, Eduardo Fernández","first_name":"Eduardo Fernández","last_name":"Ortuño"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Borrell, Víctor","first_name":"Víctor","last_name":"Borrell"}],"department":[{"_id":"SiHi"}],"date_updated":"2026-08-13T07:18:38Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.05.22.655488"}],"acknowledgement":"We thank A. Iñigo for assistance with imaging, and members of the Borrell and Herrera labs for\r\ninsightful discussions and critical reading of the manuscript. Funding to our lab members was\r\nprovided by the Spanish Research Agency (AEI): FPI contract (BES-2016-077737) to L.dV.A., FPI SO contract (SEV-2017-0723-18-1) to A.E., JdC-Incorporación contract (IJC2020-044653-I) to V.F., and JAE-Intro fellowship (JAEICU23EX_0071) to I.C., as well as by La Caixa Foundation: La Caixa-Severo Ochoa fellowship (E-03-2016-0557140) to S.A., INPhINIT-Retaining fellowship (LCF/BQ/DR21/11880012) to E.F.O., INPhINIT-Incoming fellowship (LCF/BQ/DI22/11940006) to E.N., and Junior Leader-Retaining grant to A.C. (LCF/BQ/PR23/11980051). Work was supported by grants from FWF (SFB F78) to S.H.; AEI (PID2021-125618NB-I00) and European Research Council (101118729) to V.B., who also acknowledges financial support from AEI through the “Severo Ochoa” Programme for Centers of Excellence in R&D (CEX2021-001165-S).","doi":"10.1101/2025.05.22.655488","abstract":[{"lang":"eng","text":"The cerebral cortex must contain the appropriate numbers of neurons in each layer to acquire its proper functional organization. Accordingly, neurogenesis requires precise regulation along development. Cortical neurons are made either directly by Radial Glia Cells (RGCs) that self- consume, or indirectly from RGCs via Intermediate Progenitor Cells (IPCs) and largely preserving the RGC pool. According to the standing model of cortical development, Direct Neurogenesis predominates at early stages of development, and progressively shifts to Indirect Neurogenesis, which predominates at late stages. However, neurogenesis at early stages should be compatible with RGC amplification, and neurogenesis at late stages needs to involve RGC consumption, which seems in conflict with the standing model. Here we studied the modes of neurogenesis along cortical development using multiple approaches, including birthdating, live imaging and MADM clone labeling. Contrary to the established dogma, our data show that Indirect Neurogenesis clearly predominates at early developmental stages, gradually shifting to Direct Neurogenesis at late stages. These findings challenge the current model of cortical neurogenesis, and prompt a re-evaluation of previous and ongoing work about the genetic and molecular mechanisms regulating this process."}],"type":"preprint","fulldoi":"https://doi.org/10.1101/2025.05.22.655488","project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805"}],"month":"05","title":"Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development","oa_version":"Preprint","article_processing_charge":"No","biorxivid":1,"year":"2025","date_published":"2025-05-23T00:00:00Z","language":[{"iso":"eng"}],"oa":1,"tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"status":"public","_id":"19762","citation":{"apa":"Cárdenas, A., Çelik, I., Espinós, A., Streicher, C., López-González, L., del-Valle-Anton, L., … Borrell, V. (n.d.). Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2025.05.22.655488\">https://doi.org/10.1101/2025.05.22.655488</a>","ista":"Cárdenas A, Çelik I, Espinós A, Streicher C, López-González L, del-Valle-Anton L, Fernández V, Amin S, Negri E, Ortuño EF, Hippenmeyer S, Borrell V. Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development. bioRxiv, <a href=\"https://doi.org/10.1101/2025.05.22.655488\">10.1101/2025.05.22.655488</a>.","ama":"Cárdenas A, Çelik I, Espinós A, et al. Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2025.05.22.655488\">10.1101/2025.05.22.655488</a>","mla":"Cárdenas, Adrián, et al. “Early Indirect Neurogenesis Transitions to Late Direct Neurogenesis in Mouse Cerebral Cortex Development.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2025.05.22.655488\">10.1101/2025.05.22.655488</a>.","chicago":"Cárdenas, Adrián, Irem Çelik, Alexandre Espinós, Carmen Streicher, Lara López-González, Lucia del-Valle-Anton, Virginia Fernández, et al. “Early Indirect Neurogenesis Transitions to Late Direct Neurogenesis in Mouse Cerebral Cortex Development.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2025.05.22.655488\">https://doi.org/10.1101/2025.05.22.655488</a>.","ieee":"A. Cárdenas <i>et al.</i>, “Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development,” <i>bioRxiv</i>. .","short":"A. Cárdenas, I. Çelik, A. Espinós, C. Streicher, L. López-González, L. del-Valle-Anton, V. Fernández, S. Amin, E. Negri, E.F. Ortuño, S. Hippenmeyer, V. Borrell, BioRxiv (n.d.)."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"23","publication":"bioRxiv"},{"type":"preprint","fulldoi":"https://doi.org/10.1101/2025.05.07.652665","abstract":[{"lang":"eng","text":"Radial glial progenitors (RGPs) generate all projection neurons (PNs) in the cerebral cortex through incompletely understood processes. Herein, we combine Mosaic Analysis with Double Markers (MADM)-based clonal analysis at embryonic days 12.5 and 13.5 with early postnatal callosal tracing to reveal a lineage progression that challenges the inside-outside model of cortical development and the conventional view of an invariable sequence of asymmetric neurogenic divisions. Our data demonstrate that early multipotent RGPs generate all extra-telencephalic (ET) and intra-telencephalic (IT) PNs across all layers through parallel sublineages and the random specification, during the earliest neurogenic divisions, of fate-restricted daughter RGPs. While the neuronal production of the parental multipotent RGPs consists of small ET-PN or IT-PN outputs, fate-restricted RGPs produce larger translaminar outputs spanning deep and upper layers of only IT-PNs, the predominant mammalian PN subtype. We further show that the emergence of IT-PN fate-restricted RGPs also leads to quantitatively and temporally stereotyped neurogenesis population-wise."}],"status":"public","citation":{"mla":"Varela-Martínez, I., et al. “Early Emergence of Projection-Subtype Fate-Restricted Radial Glial Progenitors Orchestrates Neocortical Neurogenesis.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2025.05.07.652665\">10.1101/2025.05.07.652665</a>.","ista":"Varela-Martínez I, Villalba Requena A, Garcia-Marqués J, Hippenmeyer S, Nieto M. Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis. bioRxiv, <a href=\"https://doi.org/10.1101/2025.05.07.652665\">10.1101/2025.05.07.652665</a>.","apa":"Varela-Martínez, I., Villalba Requena, A., Garcia-Marqués, J., Hippenmeyer, S., &#38; Nieto, M. (n.d.). Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2025.05.07.652665\">https://doi.org/10.1101/2025.05.07.652665</a>","ama":"Varela-Martínez I, Villalba Requena A, Garcia-Marqués J, Hippenmeyer S, Nieto M. Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2025.05.07.652665\">10.1101/2025.05.07.652665</a>","short":"I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer, M. Nieto, BioRxiv (n.d.).","chicago":"Varela-Martínez, I, Ana Villalba Requena, J. Garcia-Marqués, Simon Hippenmeyer, and M. Nieto. “Early Emergence of Projection-Subtype Fate-Restricted Radial Glial Progenitors Orchestrates Neocortical Neurogenesis.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2025.05.07.652665\">https://doi.org/10.1101/2025.05.07.652665</a>.","ieee":"I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer, and M. Nieto, “Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis,” <i>bioRxiv</i>. ."},"_id":"19717","title":"Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis","day":"07","publication":"bioRxiv","month":"05","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","oa_version":"Preprint","OA_place":"repository","publication_status":"submitted","department":[{"_id":"SiHi"}],"language":[{"iso":"eng"}],"date_updated":"2026-08-13T07:16:48Z","OA_type":"green","date_published":"2025-05-07T00:00:00Z","date_created":"2025-05-20T10:19:29Z","author":[{"last_name":"Varela-Martínez","first_name":"I","full_name":"Varela-Martínez, I"},{"orcid":"0000-0002-5615-5277","full_name":"Villalba Requena, Ana","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","first_name":"Ana","last_name":"Villalba Requena"},{"last_name":"Garcia-Marqués","full_name":"Garcia-Marqués, J.","first_name":"J."},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Nieto","full_name":"Nieto, M.","first_name":"M."}],"year":"2025","acknowledgement":"We thank M. Caouyette for the plasmid construction for Pou3f1 overexpression; C. Varela747 Martínez for help with the code for graphical analysis; all members from the Nieto’s lab for\r\ncomment on the manuscript, specially to F. Martín for the insightful discussions;J.C. Oliveros\r\nand J.A. García from the computational service of the CNB for help with the analysis of\r\nRNAseq dataset, C.O. Sorzano for the help with statistical analysis, and the service of\r\nAdvance Optical Microscopy of the CNB for their technical advice.\r\nI.V.M holds a fellowship funded by MCICIU (PRE-2018-083376), the work was funded by\r\nPID2020-112831GB-I00 funded by MCIN/AEI /10.13039/501100011033.\r\n","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.05.07.652665"}],"doi":"10.1101/2025.05.07.652665","oa":1},{"doi":"10.15479/AT-ISTA-20212","acknowledgement":"I would also like to\r\nthank the Austrian Academy of Sciences for awarding me a 2-year DOC fellowship\r\n(DOC26253).","publisher":"Institute of Science and Technology Austria","doi_confirm":"1","page":"119","department":[{"_id":"GradSch"},{"_id":"SiHi"}],"date_updated":"2026-10-02T12:16:56Z","author":[{"last_name":"Miranda","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","first_name":"Osvaldo","full_name":"Miranda, Osvaldo","orcid":"0000-0001-6618-6889"}],"date_created":"2025-08-22T14:07:00Z","corr_author":"1","publication_status":"published","supervisor":[{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"}],"OA_place":"publisher","title":"Unraveling the role of Pten in cortical stem cell lineage progression using MADM","keyword":["Pten","mtor","cortical development","MADM","Mapk"],"month":"08","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"17425"}]},"publication_identifier":{"isbn":["978-3-99078-063-3"],"issn":["2663-337X"]},"ddc":["570"],"project":[{"grant_number":"26253","name":"Molecular Mechanisms Regulating Cortical Neural Stem Cell Lineage Progression and Astrocyte Development","_id":"34c9fbcb-11ca-11ed-8bc3-98fa5658610d"}],"file":[{"checksum":"3331f76bbef74ff4908e2d2c9262045c","file_size":32887334,"file_id":"20230","creator":"omiranda","relation":"source_file","file_name":"2025_MirandaRomero_OsvaldoAntonio_Thesis.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2026-08-26T22:30:02Z","date_created":"2025-08-26T09:03:50Z","embargo_to":"open_access","access_level":"closed"},{"creator":"omiranda","file_size":28636240,"file_id":"20231","checksum":"02509d50cff8e35c5bcbf71e8d658176","access_level":"open_access","embargo":"2026-08-26","date_created":"2025-08-26T09:05:55Z","content_type":"application/pdf","date_updated":"2026-08-26T22:30:02Z","file_name":"2025_MirandaRomero_OsvaldoAntonio_Thesis.pdf","relation":"main_file"}],"type":"dissertation","fulldoi":"https://doi.org/10.15479/AT-ISTA-20212","abstract":[{"lang":"eng","text":"Cortical development has been studied for many decades and with each passing year, we learn \r\nmore about the processes that govern the tightly regulated developmental program. Up until \r\nrecently, the field has struggled to gain reliable access to progenitors at the single-cell level, \r\nlimiting the resolution at which we can study cortical development in vivo. Therefore, much of \r\nthe data we have on mammalian cortical development is at the cell population level. The \r\nsubsequent pages of this thesis describe novel elements of cortical development in mice; \r\nacquired using a candidate gene approach in conjunction with Mosaic Analysis with Double \r\nMarkers (MADM) to achieve single cell resolution. In this thesis, I briefly provide an overview \r\nof the state of the field, describe the methodology used to quantify morphological \r\ncharacteristics of neurons and glia, and delve into the role of Phosphatase and tensin \r\nhomologue on chromosome ten (Pten) in neurogenesis and gliogenesis in the developing mouse \r\ncortex. By using MADM to generate genetic mosaics, in which only a small fraction of cells \r\nare mutated, to study population-level changes, we can bypass the early postnatal lethality \r\nreported in Pten conditional knockouts (cKOs) using Emx1-Cre. We used Emx1-CreERT2 to \r\ninduce clonal deletion of Pten, and quantify RGP neurogenic output at the single progenitor \r\nlevel. Pten-mutant neuron populations within the mosaics were significantly expanded. In the \r\nlatter parts of this thesis, we describe how Pten deletion leads to an increase in the abundance \r\nof astrocytes. We availed ourselves of the flexibility offered by the MADM system to generate \r\nPten mosaics within a series of distinct knockout tissues to test for the interactions between \r\nPten and a battery of genes involved in distinct pro-gliogenic signaling pathways. Our survey \r\nof Pten’s interactions with genes in key signaling pathways reveals that ERK1/2 are the critical \r\neffectors downstream of EGFR signaling essential for gliogenesis. Altogether, our results \r\ndemonstrate that Pten plays critical and distinct roles throughout cortical RGP lineage \r\nprogression. "}],"oa":1,"degree_awarded":"PhD","language":[{"iso":"eng"}],"year":"2025","date_published":"2025-08-22T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"file_date_updated":"2026-08-26T22:30:02Z","article_processing_charge":"No","oa_version":"Published Version","day":"22","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","alternative_title":["ISTA Thesis"],"has_accepted_license":"1","citation":{"ama":"Miranda O. Unraveling the role of Pten in cortical stem cell lineage progression using MADM. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20212\">10.15479/AT-ISTA-20212</a>","ista":"Miranda O. 2025. Unraveling the role of Pten in cortical stem cell lineage progression using MADM. Institute of Science and Technology Austria.","apa":"Miranda, O. (2025). <i>Unraveling the role of Pten in cortical stem cell lineage progression using MADM</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20212\">https://doi.org/10.15479/AT-ISTA-20212</a>","mla":"Miranda, Osvaldo. <i>Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression Using MADM</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20212\">10.15479/AT-ISTA-20212</a>.","ieee":"O. Miranda, “Unraveling the role of Pten in cortical stem cell lineage progression using MADM,” Institute of Science and Technology Austria, 2025.","chicago":"Miranda, Osvaldo. “Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression Using MADM.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20212\">https://doi.org/10.15479/AT-ISTA-20212</a>.","short":"O. Miranda, Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression Using MADM, Institute of Science and Technology Austria, 2025."},"_id":"20212","status":"public"},{"ddc":["570"],"related_material":{"record":[{"relation":"used_in_publication","id":"17142","status":"public"}]},"license":"https://creativecommons.org/licenses/by-nc/4.0/","keyword":["ASD","periaqueductal gray","perception","behavior","potassium channels"],"title":"Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice","month":"05","type":"research_data","fulldoi":"https://doi.org/10.15479/AT:ISTA:15385","abstract":[{"lang":"eng","text":"Relevant information about the data can be found in the 'Readme_Data.txt' file. \r\nA previous version of the publication can be found on BioRxiv: https://www.biorxiv.org/content/10.1101/2022.10.11.511691v4\r\nand published in Plos Biology (2024)"}],"file":[{"date_created":"2024-05-15T06:09:17Z","success":1,"date_updated":"2024-05-15T06:09:17Z","content_type":"application/zip","access_level":"open_access","relation":"main_file","file_name":"PatchClamp.zip","creator":"mjoesch","checksum":"9205eb0876f0f08552dbad80d6884b4b","file_id":"15396","file_size":"1149617663"},{"creator":"mjoesch","file_size":"564903112","file_id":"15397","access_level":"open_access","date_updated":"2024-05-15T06:09:12Z","content_type":"application/zip","success":1,"date_created":"2024-05-15T06:09:12Z","file_name":"SiliconProbe.zip","relation":"main_file"},{"creator":"mjoesch","file_id":"15398","file_size":"11685703","checksum":"49a807bbab06b5fada38f532e2176e2e","access_level":"open_access","date_updated":"2024-05-15T06:09:14Z","content_type":"application/zip","date_created":"2024-05-15T06:09:14Z","success":1,"file_name":"WesternBlot.zip","relation":"main_file"},{"file_name":"Behaviour.zip","relation":"main_file","access_level":"open_access","date_updated":"2024-05-15T06:09:38Z","content_type":"application/zip","date_created":"2024-05-15T06:09:38Z","success":1,"file_size":"1335626779","file_id":"15399","checksum":"beeeeaa43770090f3b291209ed6b0623","creator":"mjoesch"},{"access_level":"open_access","date_updated":"2024-05-16T09:08:20Z","content_type":"text/plain","date_created":"2024-05-16T09:08:20Z","success":1,"file_name":"Readme_Data.txt","relation":"main_file","creator":"mjoesch","file_id":"15400","file_size":18841,"checksum":"8862ad7719388304d1d19f8e7db8bb00"}],"date_updated":"2026-10-21T08:31:42Z","department":[{"_id":"MaJö"},{"_id":"PreCl"},{"_id":"SiHi"},{"_id":"RySh"},{"_id":"GaNo"}],"author":[{"last_name":"Burnett","orcid":"0000-0002-8937-410X","full_name":"Burnett, Laura","id":"3B717F68-F248-11E8-B48F-1D18A9856A87","first_name":"Laura"},{"orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter","last_name":"Koppensteiner"},{"last_name":"Symonova","orcid":"0000-0003-2012-9947","full_name":"Symonova, Olga","id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87","first_name":"Olga"},{"id":"93ac43e8-8599-11eb-9b86-f6efb0a4c207","first_name":"Tomas","full_name":"Masson, Tomas","orcid":"0000-0002-2634-6283","last_name":"Masson"},{"last_name":"Vega Zuniga","full_name":"Vega Zuniga, Tomas A","id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87","first_name":"Tomas A"},{"full_name":"Contreras, Ximena","first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","last_name":"Contreras"},{"full_name":"Rülicke, Thomas","first_name":"Thomas","last_name":"Rülicke"},{"last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi"},{"last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","first_name":"Maximilian A","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330"}],"date_created":"2024-05-13T15:04:04Z","publisher":"Institute of Science and Technology Austria","acknowledgement":"We thank Armel Nicolas, Bella Bruszel and Ewelina Dutkiewicz from the ISTA Mass Spectrometry Service (Lab Services Facilities) for all Proteomics work, including samples preparation, LC/MS data acquisition, searches and data evaluation. We thank Prof. Peter Jonas for his suggestion on the involvement of potassium channels and members of the Neuroethology group for their comments on the manuscript. Katalin Szigeti and Julie Murmann for experimental help. This research was supported by the Scientific Service Units of ISTA through resources provided by the Lab Support Facility, the Imaging and Optics Facility, the Machine Shop Unit and the Preclinical Facility, especially Freyja Langer and Michael Schunn. ","doi":"10.15479/AT:ISTA:15385","corr_author":"1","has_accepted_license":"1","day":"15","user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","tmp":{"image":"/images/cc_by_nc.png","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"status":"public","citation":{"mla":"Burnett, Laura, et al. <i>Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>.","ista":"Burnett L, Koppensteiner P, Symonova O, Masson T, Vega Zuniga TA, Contreras X, Rülicke T, Shigemoto R, Novarino G, Jösch MA. 2024. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>.","apa":"Burnett, L., Koppensteiner, P., Symonova, O., Masson, T., Vega Zuniga, T. A., Contreras, X., … Jösch, M. A. (2024). Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">https://doi.org/10.15479/AT:ISTA:15385</a>","ama":"Burnett L, Koppensteiner P, Symonova O, et al. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. 2024. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>","short":"L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X. Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, (2024).","chicago":"Burnett, Laura, Peter Koppensteiner, Olga Symonova, Tomas Masson, Tomas A Vega Zuniga, Ximena Contreras, Thomas Rülicke, Ryuichi Shigemoto, Gaia Novarino, and Maximilian A Jösch. “Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">https://doi.org/10.15479/AT:ISTA:15385</a>.","ieee":"L. Burnett <i>et al.</i>, “Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice.” Institute of Science and Technology Austria, 2024."},"_id":"15385","date_published":"2024-05-15T00:00:00Z","year":"2024","oa":1,"article_processing_charge":"No","oa_version":"Published Version","file_date_updated":"2024-05-16T09:08:20Z","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"Bio"}]},{"language":[{"iso":"eng"}],"pmid":1,"year":"2024","date_published":"2024-03-15T00:00:00Z","oa":1,"article_processing_charge":"Yes (in subscription journal)","oa_version":"Published Version","das_tickbox":"1","researchdata_availability":"not applicable","file_date_updated":"2024-07-16T11:50:03Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"dataavailabilitystatement":"No custom code or dataset was generated in this protocol.","has_accepted_license":"1","article_number":"102771","ec_funded":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","article_type":"review","publication":"STAR Protocols","day":"15","scopus_import":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","quality_controlled":"1","citation":{"mla":"Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>, vol. 5, no. 1, 102771, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>.","apa":"Amberg, N., Cheung, G. T., &#38; Hippenmeyer, S. (2024). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>","ista":"Amberg N, Cheung GT, Hippenmeyer S. 2024. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 5(1), 102771.","ama":"Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. 2024;5(1). doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>","short":"N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2024).","chicago":"Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>.","ieee":"N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry,” <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2024."},"_id":"14683","intvolume":"         5","date_updated":"2026-10-21T08:40:15Z","department":[{"_id":"SiHi"}],"date_created":"2023-12-13T11:48:05Z","author":[{"last_name":"Amberg","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole"},{"last_name":"Cheung","full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer"}],"publisher":"Elsevier","acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging & Optics Facility (IOF) and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme (T 1031). G.C. received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411 as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","doi":"10.1016/j.xpro.2023.102771","publication_status":"published","issue":"1","external_id":{"pmid":["38070137"]},"corr_author":"1","supplementarymaterial":"no","ddc":["570"],"publication_identifier":{"issn":["2666-1667"]},"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"title":"Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry","month":"03","type":"journal_article","fulldoi":"https://doi.org/10.1016/j.xpro.2023.102771","volume":5,"abstract":[{"text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.\r\nFor complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1","lang":"eng"}],"file":[{"relation":"main_file","file_name":"2024_STARProtoc_Amberg.pdf","date_updated":"2024-07-16T11:50:03Z","content_type":"application/pdf","date_created":"2024-07-16T11:50:03Z","success":1,"access_level":"open_access","checksum":"3f0ee62e04bf5a44b45b035662826e95","file_size":8871807,"file_id":"17260","creator":"dernst"}],"project":[{"name":"Role of Eed in neural stem cell lineage progression","grant_number":"T01031","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}]},{"APC_amount":"804 EUR","oa":1,"date_published":"2024-09-20T00:00:00Z","year":"2024","language":[{"iso":"eng"}],"pmid":1,"file_date_updated":"2025-01-09T12:12:40Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"das_tickbox":"1","oa_version":"Published Version","article_processing_charge":"Yes","researchdata_availability":"yes (supplementary data)","publication":"STAR Protocols","day":"20","article_type":"original","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","dataavailabilitystatement":"No dataset was generated while composing this protocol. A FIJI macro script “3DSerialSectionAlignmentLineROI.ijm” and a Microsoft Excel template used in this protocol are provided as supplementary materials.","ec_funded":1,"has_accepted_license":"1","article_number":"103157","quality_controlled":"1","status":"public","_id":"17187","citation":{"short":"G.T. Cheung, C. Streicher, S. Hippenmeyer, STAR Protocols 5 (2024).","ieee":"G. T. Cheung, C. Streicher, and S. Hippenmeyer, “Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice,” <i>STAR Protocols</i>, vol. 5, no. 3. Elsevier, 2024.","chicago":"Cheung, Giselle T, Carmen Streicher, and Simon Hippenmeyer. “Protocol for Quantitative Reconstruction of Cell Lineage Using Mosaic Analysis with Double Markers in Mice.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2024.103157\">https://doi.org/10.1016/j.xpro.2024.103157</a>.","mla":"Cheung, Giselle T., et al. “Protocol for Quantitative Reconstruction of Cell Lineage Using Mosaic Analysis with Double Markers in Mice.” <i>STAR Protocols</i>, vol. 5, no. 3, 103157, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103157\">10.1016/j.xpro.2024.103157</a>.","ista":"Cheung GT, Streicher C, Hippenmeyer S. 2024. Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice. STAR Protocols. 5(3), 103157.","apa":"Cheung, G. T., Streicher, C., &#38; Hippenmeyer, S. (2024). Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2024.103157\">https://doi.org/10.1016/j.xpro.2024.103157</a>","ama":"Cheung GT, Streicher C, Hippenmeyer S. Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice. <i>STAR Protocols</i>. 2024;5(3). doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103157\">10.1016/j.xpro.2024.103157</a>"},"scopus_import":"1","tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"acknowledgement":"We thank A. Heger for mouse breeding support. This work was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging & Optics and Preclinical facilities. G.C. received funding from the European Commission (IST plus postdoctoral fellowship); S.H. was funded by ISTA institutional funds and the Austrian Science Fund Special Research Programmes (FWF SFB-F78 Neuro Stem Modulation).","doi":"10.1016/j.xpro.2024.103157","author":[{"id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T","last_name":"Cheung"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen","full_name":"Streicher, Carmen","last_name":"Streicher"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"OA_type":"gold","date_created":"2024-06-30T22:01:04Z","department":[{"_id":"SiHi"}],"date_updated":"2026-10-21T09:14:52Z","intvolume":"         5","publisher":"Elsevier","external_id":{"pmid":["38935508"]},"corr_author":"1","issue":"3","supplementarymaterial":"yes","OA_place":"publisher","publication_status":"published","publication_identifier":{"eissn":["2666-1667"]},"month":"09","title":"Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice","ddc":["570"],"project":[{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"}],"file":[{"relation":"main_file","file_name":"2024_STARProtoc_Cheung.pdf","date_created":"2025-01-09T12:12:40Z","success":1,"content_type":"application/pdf","date_updated":"2025-01-09T12:12:40Z","access_level":"open_access","checksum":"d8a8cdba82a394e731aa699ace1ae433","file_id":"18809","file_size":5186071,"creator":"dernst"}],"abstract":[{"text":"The generation of diverse cell types during development is fundamental to brain\r\nfunctions. We outline a protocol to quantitatively assess the clonal output of individual neural progenitors using mosaic analysis with double markers (MADM) in\r\nmice. We first describe steps to acquire and reconstruct adult MADM clones in\r\nthe superior colliculus. Then we detail analysis pipelines to determine clonal\r\ncomposition and architecture. This protocol enables the buildup of quantitative\r\nframeworks of lineage progression with precise spatial resolution in the brain.\r\nFor complete details on the use and execution of this protocol, please refer to\r\nCheung et al.1","lang":"eng"}],"volume":5,"fulldoi":"https://doi.org/10.1016/j.xpro.2024.103157","type":"journal_article"},{"publication_status":"published","OA_place":"publisher","supplementarymaterial":"no","corr_author":"1","external_id":{"pmid":["38968076"]},"issue":"3","publisher":"Elsevier","OA_type":"gold","date_created":"2024-07-14T22:01:10Z","author":[{"last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T"},{"full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","last_name":"Pauler"},{"last_name":"Koppensteiner","first_name":"Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer"}],"date_updated":"2026-10-21T09:15:51Z","department":[{"_id":"SiHi"},{"_id":"PreCl"}],"intvolume":"         5","doi":"10.1016/j.xpro.2024.103168","acknowledgement":"We thank R. Beattie and T. Asenov for designing and producing components of the multi-well slice recover chamber. We thank R. Shigemoto for providing equipment access. We thank C. Streicher and A. Heger for mouse breeding support. This work was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging & Optics, Miba Machine Shop, and Preclinical facilities. G.C. received funding from the European Commission (IST plus postdoctoral fellowship) and S.H. was funded by ISTA institutional funds and the Austrian Science Fund Special Research Programmes (FWF SFB-F78 Neuro Stem Modulation).","volume":5,"abstract":[{"lang":"eng","text":"The lineage relationship of clonally-related cells offers important insights into the ontogeny and cytoarchitecture of the brain in health and disease. Here, we provide a protocol to concurrently assess cell lineage relationship and cell-type identity among clonally-related cells in situ. We first describe the preparation and screening of acute brain slices containing clonally-related cells labeled using mosaic analysis with double markers (MADM). We then outline steps to collect RNA from individual cells for downstream applications and cell-type identification using RNA sequencing.\r\nFor complete details on the use and execution of this protocol, please refer to Cheung et al.\r\n1"}],"fulldoi":"https://doi.org/10.1016/j.xpro.2024.103168","type":"journal_article","file":[{"file_name":"2024_STARProtoc_Cheung2.pdf","relation":"main_file","access_level":"open_access","date_updated":"2025-01-09T12:16:53Z","content_type":"application/pdf","success":1,"date_created":"2025-01-09T12:16:53Z","file_size":6445556,"file_id":"18810","checksum":"464f52ecc6ec92f509552823bb82bf79","creator":"dernst"}],"project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805"}],"ddc":["570"],"month":"09","title":"Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq","publication_identifier":{"eissn":["2666-1667"]},"researchdata_availability":"not applicable","oa_version":"Published Version","das_tickbox":"1","article_processing_charge":"Yes","acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"PreCl"}],"file_date_updated":"2025-01-09T12:16:53Z","year":"2024","date_published":"2024-09-20T00:00:00Z","pmid":1,"language":[{"iso":"eng"}],"oa":1,"APC_amount":"804 EUR","tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"scopus_import":"1","_id":"17232","citation":{"apa":"Cheung, G. T., Pauler, F., Koppensteiner, P., &#38; Hippenmeyer, S. (2024). Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">https://doi.org/10.1016/j.xpro.2024.103168</a>","ista":"Cheung GT, Pauler F, Koppensteiner P, Hippenmeyer S. 2024. Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. STAR Protocols. 5(3), 103168.","ama":"Cheung GT, Pauler F, Koppensteiner P, Hippenmeyer S. Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. <i>STAR Protocols</i>. 2024;5(3). doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">10.1016/j.xpro.2024.103168</a>","mla":"Cheung, Giselle T., et al. “Protocol for Mapping Cell Lineage and Cell-Type Identity of Clonally-Related Cells in Situ Using MADM-CloneSeq.” <i>STAR Protocols</i>, vol. 5, no. 3, 103168, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">10.1016/j.xpro.2024.103168</a>.","ieee":"G. T. Cheung, F. Pauler, P. Koppensteiner, and S. Hippenmeyer, “Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq,” <i>STAR Protocols</i>, vol. 5, no. 3. Elsevier, 2024.","chicago":"Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, and Simon Hippenmeyer. “Protocol for Mapping Cell Lineage and Cell-Type Identity of Clonally-Related Cells in Situ Using MADM-CloneSeq.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">https://doi.org/10.1016/j.xpro.2024.103168</a>.","short":"G.T. Cheung, F. Pauler, P. Koppensteiner, S. Hippenmeyer, STAR Protocols 5 (2024)."},"quality_controlled":"1","status":"public","article_number":"103168","has_accepted_license":"1","dataavailabilitystatement":"No dataset or new code was generated while composing this protocol.","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","article_type":"original","publication":"STAR Protocols","day":"20"},{"project":[{"name":"Molecular mechanisms of radial neuronal migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"file":[{"content_type":"application/pdf","date_updated":"2024-07-16T12:04:46Z","success":1,"date_created":"2024-07-16T12:04:46Z","access_level":"open_access","relation":"main_file","file_name":"2024_STARProtoc_Hansen.pdf","creator":"dernst","checksum":"4644d537451c5c114a9d7c7829b65bba","file_size":3758943,"file_id":"17264"}],"abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) technology enables the sparse labeling of genetically defined neurons. We present a protocol for time-lapse imaging of cortical projection neuron migration in mice using MADM. We describe steps for the isolation, culturing, and 4D imaging of neuronal dynamics in MADM-labeled brain tissue. While this protocol is compatible with other single-cell labeling methods, the MADM approach provides a genetic platform for the functional assessment of cell-autonomous candidate gene function and the relative contribution of non-cell-autonomous effects.\r\n\r\nFor complete details on the use and execution of this protocol, please refer to Hansen et al. (2022),1 Contreras et al. (2021),2 and Amberg and Hippenmeyer (2021).3"}],"volume":5,"fulldoi":"https://doi.org/10.1016/j.xpro.2023.102795","type":"journal_article","publication_identifier":{"eissn":["2666-1667"]},"related_material":{"link":[{"relation":"software","url":"http://github.com/hippenmeyerlab"}]},"month":"03","title":"Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers","ddc":["570"],"external_id":{"pmid":["38165800"]},"corr_author":"1","issue":"1","supplementarymaterial":"no","publication_status":"published","acknowledgement":"We thank Florian Pauler for discussion and his expert technical support. This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging and Optics Facility (IOF) and Preclinical Facility (PCF). A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences.","doi":"10.1016/j.xpro.2023.102795","author":[{"first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H","last_name":"Hansen"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"}],"date_created":"2024-01-14T23:00:56Z","intvolume":"         5","date_updated":"2026-10-21T09:13:13Z","department":[{"_id":"SiHi"}],"publisher":"Elsevier","quality_controlled":"1","status":"public","_id":"14794","citation":{"ama":"Hansen AH, Hippenmeyer S. Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. <i>STAR Protocols</i>. 2024;5(1). doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102795\">10.1016/j.xpro.2023.102795</a>","apa":"Hansen, A. H., &#38; Hippenmeyer, S. (2024). Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2023.102795\">https://doi.org/10.1016/j.xpro.2023.102795</a>","ista":"Hansen AH, Hippenmeyer S. 2024. Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. STAR Protocols. 5(1), 102795.","mla":"Hansen, Andi H., and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>, vol. 5, no. 1, 102795, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102795\">10.1016/j.xpro.2023.102795</a>.","chicago":"Hansen, Andi H, and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2023.102795\">https://doi.org/10.1016/j.xpro.2023.102795</a>.","ieee":"A. H. Hansen and S. Hippenmeyer, “Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers,” <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2024.","short":"A.H. Hansen, S. Hippenmeyer, STAR Protocols 5 (2024)."},"scopus_import":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publication":"STAR Protocols","day":"15","article_type":"review","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","dataavailabilitystatement":"All scripts that were used to prepare data and figures for this manuscript are available via GitHub at http://github.com/hippenmeyerlab. GitHub DOI is listed in the key resources table. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.","article_number":"102795","has_accepted_license":"1","file_date_updated":"2024-07-16T12:04:46Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"das_tickbox":"1","oa_version":"Published Version","article_processing_charge":"Yes","researchdata_availability":"yes","oa":1,"year":"2024","date_published":"2024-03-15T00:00:00Z","language":[{"iso":"eng"}],"pmid":1},{"dataavailabilitystatement":"All data generated and analyzed in this study are included in the paper and/or supplementary materials. Raw sequencing data has been deposited at Gene Expression Omnibus (GEO). All scripts that were used to prepare data and figures for this manuscript are available via GitHub at https://github.com/fpauler. Accession numbers and github DOI are listed in the key resources table. Files for 3D printing of acute slice recovery chamber (3D model 361319) are deposited to https://www.printables.com.","has_accepted_license":"1","article_type":"original","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","day":"17","publication":"Neuron","scopus_import":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","quality_controlled":"1","citation":{"short":"G.T. Cheung, F. Pauler, P. Koppensteiner, T. Krausgruber, C. Streicher, M. Schrammel, N.Y. Özgen, A. Ivec, C. Bock, R. Shigemoto, S. Hippenmeyer, Neuron 112 (2024) 230–246.e11.","chicago":"Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, Thomas Krausgruber, Carmen Streicher, Martin Schrammel, Natalie Y Özgen, et al. “Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus.” <i>Neuron</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">https://doi.org/10.1016/j.neuron.2023.11.009</a>.","ieee":"G. T. Cheung <i>et al.</i>, “Multipotent progenitors instruct ontogeny of the superior colliculus,” <i>Neuron</i>, vol. 112, no. 2. Elsevier, p. 230–246.e11, 2024.","mla":"Cheung, Giselle T., et al. “Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus.” <i>Neuron</i>, vol. 112, no. 2, Elsevier, 2024, p. 230–246.e11, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">10.1016/j.neuron.2023.11.009</a>.","ista":"Cheung GT, Pauler F, Koppensteiner P, Krausgruber T, Streicher C, Schrammel M, Özgen NY, Ivec A, Bock C, Shigemoto R, Hippenmeyer S. 2024. Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. 112(2), 230–246.e11.","apa":"Cheung, G. T., Pauler, F., Koppensteiner, P., Krausgruber, T., Streicher, C., Schrammel, M., … Hippenmeyer, S. (2024). Multipotent progenitors instruct ontogeny of the superior colliculus. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">https://doi.org/10.1016/j.neuron.2023.11.009</a>","ama":"Cheung GT, Pauler F, Koppensteiner P, et al. Multipotent progenitors instruct ontogeny of the superior colliculus. <i>Neuron</i>. 2024;112(2):230-246.e11. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">10.1016/j.neuron.2023.11.009</a>"},"_id":"12875","pmid":1,"language":[{"iso":"eng"}],"date_published":"2024-01-17T00:00:00Z","year":"2024","oa":1,"article_processing_charge":"Yes (via OA deal)","das_tickbox":"1","oa_version":"Published Version","researchdata_availability":"yes","file_date_updated":"2024-02-06T13:56:15Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"PreCl"}],"ddc":["570"],"related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-pedigree-of-brain-cells/","description":"News on ISTA Website","relation":"press_release"}]},"publication_identifier":{"issn":["0896-6273"]},"title":"Multipotent progenitors instruct ontogeny of the superior colliculus","month":"01","fulldoi":"https://doi.org/10.1016/j.neuron.2023.11.009","type":"journal_article","abstract":[{"lang":"eng","text":"The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and is composed of a rich diversity of excitatory and inhibitory neurons and glia. However, the developmental principles directing the generation of SC cell-type diversity are not understood. Here, we pursued systematic cell lineage tracing in silico and in vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal analysis with single-cell sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron types, even at the stage of terminal division. While individual clonal units show no pre-defined cellular composition, the establishment of appropriate relative proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively, our findings provide an inaugural framework at the single-RGP/-cell level of the mammalian SC ontogeny."}],"volume":112,"project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805"}],"file":[{"file_name":"2024_Neuron_Cheung.pdf","relation":"main_file","access_level":"open_access","content_type":"application/pdf","date_updated":"2024-02-06T13:56:15Z","success":1,"date_created":"2024-02-06T13:56:15Z","file_size":5942467,"file_id":"14944","checksum":"32b3788f7085cf44a84108d8faaff3ce","creator":"dernst"}],"intvolume":"       112","date_updated":"2026-10-21T09:51:58Z","department":[{"_id":"SiHi"},{"_id":"RySh"}],"date_created":"2023-04-27T09:41:48Z","author":[{"orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T","first_name":"Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","last_name":"Cheung"},{"last_name":"Pauler","first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048"},{"last_name":"Koppensteiner","first_name":"Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948"},{"first_name":"Thomas","full_name":"Krausgruber, Thomas","last_name":"Krausgruber"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"full_name":"Schrammel, Martin","id":"f13e7cae-e8bd-11ed-841a-96dedf69f46d","first_name":"Martin","last_name":"Schrammel"},{"id":"e68ece33-f6e0-11ea-865d-ae1031dcc090","first_name":"Natalie Y","full_name":"Özgen, Natalie Y","last_name":"Özgen"},{"first_name":"Alexis","id":"1d144691-e8be-11ed-9b33-bdd3077fad4c","full_name":"Ivec, Alexis","last_name":"Ivec"},{"last_name":"Bock","first_name":"Christoph","full_name":"Bock, Christoph"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"publisher":"Elsevier","page":"230-246.e11","acknowledgement":"We thank Liqun Luo for his continued support, for providing essential resources for generating Fzd10-CreER mice which were generated in his laboratory, and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic mouse line for this study; A. Heger for mouse colony management; R. Beattie and T. Asenov for designing and producing components of acute slice recovery chamber for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial experiments, technical support and/or assistance. This study was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds; the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H. ","doi":"10.1016/j.neuron.2023.11.009","isi":1,"publication_status":"published","issue":"2","external_id":{"isi":["001163937900001"],"pmid":["38096816"]},"corr_author":"1","supplementarymaterial":"yes"},{"alternative_title":["Methods in Molecular Biology"],"editor":[{"last_name":"Toyooka","full_name":"Toyooka, Kazuhito","first_name":"Kazuhito"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","day":"13","publication":"Neuronal Morphogenesis","scopus_import":"1","quality_controlled":"1","status":"public","_id":"17425","citation":{"apa":"Miranda, O., Cheung, G. T., &#38; Hippenmeyer, S. (2024). Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers. In K. Toyooka (Ed.), <i>Neuronal Morphogenesis</i> (1st ed., Vol. 2831, pp. 283–299). New York, NY: Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-3969-6_19\">https://doi.org/10.1007/978-1-0716-3969-6_19</a>","ista":"Miranda O, Cheung GT, Hippenmeyer S. 2024.Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers. In: Neuronal Morphogenesis. Methods in Molecular Biology, vol. 2831, 283–299.","ama":"Miranda O, Cheung GT, Hippenmeyer S. Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers. In: Toyooka K, ed. <i>Neuronal Morphogenesis</i>. Vol 2831. 1st ed. MIMB. New York, NY: Springer Nature; 2024:283-299. doi:<a href=\"https://doi.org/10.1007/978-1-0716-3969-6_19\">10.1007/978-1-0716-3969-6_19</a>","mla":"Miranda, Osvaldo, et al. “Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers.” <i>Neuronal Morphogenesis</i>, edited by Kazuhito Toyooka, 1st ed., vol. 2831, Springer Nature, 2024, pp. 283–99, doi:<a href=\"https://doi.org/10.1007/978-1-0716-3969-6_19\">10.1007/978-1-0716-3969-6_19</a>.","chicago":"Miranda, Osvaldo, Giselle T Cheung, and Simon Hippenmeyer. “Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers.” In <i>Neuronal Morphogenesis</i>, edited by Kazuhito Toyooka, 1st ed., 2831:283–99. MIMB. New York, NY: Springer Nature, 2024. <a href=\"https://doi.org/10.1007/978-1-0716-3969-6_19\">https://doi.org/10.1007/978-1-0716-3969-6_19</a>.","ieee":"O. Miranda, G. T. Cheung, and S. Hippenmeyer, “Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers,” in <i>Neuronal Morphogenesis</i>, 1st ed., vol. 2831, K. Toyooka, Ed. New York, NY: Springer Nature, 2024, pp. 283–299.","short":"O. Miranda, G.T. Cheung, S. Hippenmeyer, in:, K. Toyooka (Ed.), Neuronal Morphogenesis, 1st ed., Springer Nature, New York, NY, 2024, pp. 283–299."},"year":"2024","date_published":"2024-08-13T00:00:00Z","language":[{"iso":"eng"}],"pmid":1,"series_title":"MIMB","oa_version":"None","das_tickbox":"0","article_processing_charge":"No","researchdata_availability":"no","acknowledged_ssus":[{"_id":"Bio"}],"place":"New York, NY","publication_identifier":{"isbn":["9781071639689"],"eisbn":["9781071639696"],"issn":["1064-3745"],"eissn":["1940-6029"]},"related_material":{"record":[{"relation":"dissertation_contains","id":"20212","status":"public"}]},"month":"08","title":"Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers","volume":2831,"abstract":[{"text":"Mosaic Analysis with Double Markers (MADM) is a powerful genetic method typically used for lineage tracing and to disentangle cell autonomous and tissue-wide roles of candidate genes with single cell resolution. Given the relatively sparse labeling, depending on which of the 19 MADM chromosomes one chooses, the MADM approach represents the perfect opportunity for cell morphology analysis. Various MADM studies include reports of morphological anomalies and phenotypes in the central nervous system (CNS). MADM for any candidate gene can easily incorporate morphological analysis within the experimental workflow. Here, we describe the methods of morphological cell analysis which we developed in the course of diverse recent MADM studies. This chapter will specifically focus on methods to quantify aspects of the morphology of neurons and astrocytes within the CNS, but these methods can broadly be applied to any MADM-labeled cells throughout the entire organism. We will cover two analyses—soma volume and dendrite characterization—of physical characteristics of pyramidal neurons in the somatosensory cortex, and two analyses—volume and Sholl analysis—of astrocyte morphology.","lang":"eng"}],"fulldoi":"https://doi.org/10.1007/978-1-0716-3969-6_19","type":"book_chapter","project":[{"name":"Molecular Mechanisms Regulating Cortical Neural Stem Cell Lineage Progression and Astrocyte Development","grant_number":"26253","_id":"34c9fbcb-11ca-11ed-8bc3-98fa5658610d"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"}],"date_created":"2024-08-13T12:16:41Z","author":[{"last_name":"Miranda","first_name":"Osvaldo","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","orcid":"0000-0001-6618-6889","full_name":"Miranda, Osvaldo"},{"last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T"},{"last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"}],"date_updated":"2026-11-11T23:31:18Z","intvolume":"      2831","department":[{"_id":"GradSch"},{"_id":"SiHi"}],"page":"283-299","edition":"1","publisher":"Springer Nature","acknowledgement":"We thank all Hippenmeyer lab members for support and discussions. This work was supported by the Scientific Service Units (SSU) at ISTA through resources provided by the Imaging & Optics Facility (IOF). O.A.M was a recipient of a DOC Fellowship (26253) of the Austrian Academy of Sciences. This work was supported by ISTA institutional funds, and The Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H.","doi":"10.1007/978-1-0716-3969-6_19","publication_status":"published","corr_author":"1","external_id":{"pmid":["39134857"]},"supplementarymaterial":"yes"},{"_id":"12542","citation":{"mla":"Villalba Requena, Ana, and Simon Hippenmeyer. “Going Back in Time with TEMPO.” <i>Neuron</i>, vol. 111, no. 3, Elsevier, 2023, pp. 291–93, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.01.006\">10.1016/j.neuron.2023.01.006</a>.","apa":"Villalba Requena, A., &#38; Hippenmeyer, S. (2023). Going back in time with TEMPO. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.01.006\">https://doi.org/10.1016/j.neuron.2023.01.006</a>","ista":"Villalba Requena A, Hippenmeyer S. 2023. Going back in time with TEMPO. Neuron. 111(3), 291–293.","ama":"Villalba Requena A, Hippenmeyer S. Going back in time with TEMPO. <i>Neuron</i>. 2023;111(3):291-293. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.01.006\">10.1016/j.neuron.2023.01.006</a>","short":"A. Villalba Requena, S. Hippenmeyer, Neuron 111 (2023) 291–293.","chicago":"Villalba Requena, Ana, and Simon Hippenmeyer. “Going Back in Time with TEMPO.” <i>Neuron</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.neuron.2023.01.006\">https://doi.org/10.1016/j.neuron.2023.01.006</a>.","ieee":"A. Villalba Requena and S. Hippenmeyer, “Going back in time with TEMPO,” <i>Neuron</i>, vol. 111, no. 3. Elsevier, pp. 291–293, 2023."},"quality_controlled":"1","status":"public","scopus_import":"1","article_type":"letter_note","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Neuron","day":"01","oa_version":"Published Version","article_processing_charge":"No","oa":1,"date_published":"2023-02-01T00:00:00Z","year":"2023","pmid":1,"language":[{"iso":"eng"}],"abstract":[{"text":"In this issue of Neuron, Espinosa-Medina et al.1 present the TEMPO (Temporal Encoding and Manipulation in a Predefined Order) system, which enables the marking and genetic manipulation of sequentially generated cell lineages in vertebrate species in vivo.","lang":"eng"}],"volume":111,"fulldoi":"https://doi.org/10.1016/j.neuron.2023.01.006","type":"journal_article","month":"02","title":"Going back in time with TEMPO","publication_identifier":{"eissn":["1097-4199"]},"ddc":["570"],"corr_author":"1","external_id":{"pmid":["36731425"],"isi":["000994473300001"]},"issue":"3","publication_status":"published","OA_place":"publisher","isi":1,"doi":"10.1016/j.neuron.2023.01.006","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.neuron.2023.01.006"}],"page":"291-293","publisher":"Elsevier","OA_type":"free access","date_created":"2023-02-12T23:00:58Z","author":[{"id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","first_name":"Ana","full_name":"Villalba Requena, Ana","orcid":"0000-0002-5615-5277","last_name":"Villalba Requena"},{"last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"}],"department":[{"_id":"SiHi"}],"intvolume":"       111","date_updated":"2026-06-18T17:27:44Z"},{"day":"01","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication":"Journal of Neurophysiology","article_type":"original","status":"public","quality_controlled":"1","citation":{"short":"D.R. Ladle, S. Hippenmeyer, Journal of Neurophysiology 129 (2023) 501–512.","ieee":"D. R. Ladle and S. Hippenmeyer, “Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons,” <i>Journal of Neurophysiology</i>, vol. 129, no. 3. American Physiological Society, pp. 501–512, 2023.","chicago":"Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” <i>Journal of Neurophysiology</i>. American Physiological Society, 2023. <a href=\"https://doi.org/10.1152/jn.00172.2022\">https://doi.org/10.1152/jn.00172.2022</a>.","mla":"Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” <i>Journal of Neurophysiology</i>, vol. 129, no. 3, American Physiological Society, 2023, pp. 501–12, doi:<a href=\"https://doi.org/10.1152/jn.00172.2022\">10.1152/jn.00172.2022</a>.","ama":"Ladle DR, Hippenmeyer S. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. <i>Journal of Neurophysiology</i>. 2023;129(3):501-512. doi:<a href=\"https://doi.org/10.1152/jn.00172.2022\">10.1152/jn.00172.2022</a>","ista":"Ladle DR, Hippenmeyer S. 2023. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology. 129(3), 501–512.","apa":"Ladle, D. R., &#38; Hippenmeyer, S. (2023). Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. <i>Journal of Neurophysiology</i>. American Physiological Society. <a href=\"https://doi.org/10.1152/jn.00172.2022\">https://doi.org/10.1152/jn.00172.2022</a>"},"_id":"12562","scopus_import":"1","pmid":1,"language":[{"iso":"eng"}],"year":"2023","date_published":"2023-03-01T00:00:00Z","article_processing_charge":"No","oa_version":"None","publication_identifier":{"eissn":["1522-1598"],"issn":["0022-3077"]},"title":"Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons","keyword":["Physiology","General Neuroscience"],"month":"03","fulldoi":"https://doi.org/10.1152/jn.00172.2022","type":"journal_article","abstract":[{"lang":"eng","text":"Presynaptic inputs determine the pattern of activation of postsynaptic neurons in a neural circuit. Molecular and genetic pathways that regulate the selective formation of subsets of presynaptic inputs are largely unknown, despite significant understanding of the general process of synaptogenesis. In this study, we have begun to identify such factors using the spinal monosynaptic stretch reflex circuit as a model system. In this neuronal circuit, Ia proprioceptive afferents establish monosynaptic connections with spinal motor neurons that project to the same muscle (termed homonymous connections) or muscles with related or synergistic function. However, monosynaptic connections are not formed with motor neurons innervating muscles with antagonistic functions. The ETS transcription factor ER81 (also known as ETV1) is expressed by all proprioceptive afferents, but only a small set of motor neuron pools in the lumbar spinal cord of the mouse. Here we use conditional mouse genetic techniques to eliminate Er81 expression selectively from motor neurons. We find that ablation of Er81 in motor neurons reduces synaptic inputs from proprioceptive afferents conveying information from homonymous and synergistic muscles, with no change observed in the connectivity pattern from antagonistic proprioceptive afferents. In summary, these findings suggest a role for ER81 in defined motor neuron pools to control the assembly of specific presynaptic inputs and thereby influence the profile of activation of these motor neurons."}],"volume":129,"acknowledgement":"The authors gratefully thank Dr. Silvia Arber, University of Basel and Friedrich Miescher Institute for Biomedical Research, for support and in whose lab the data were collected. For advice on statistical analysis, we thank Michael Bottomley from the Statistical Consulting Center, College of Science and Mathematics, Wright State University.","doi":"10.1152/jn.00172.2022","department":[{"_id":"SiHi"}],"intvolume":"       129","date_updated":"2024-10-21T06:01:28Z","date_created":"2023-02-15T14:46:14Z","author":[{"last_name":"Ladle","full_name":"Ladle, David R.","first_name":"David R."},{"last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"}],"publisher":"American Physiological Society","page":"501-512","issue":"3","external_id":{"pmid":["36695533"],"isi":["000957721600001"]},"isi":1,"publication_status":"published"},{"oa":1,"language":[{"iso":"eng"}],"pmid":1,"year":"2023","date_published":"2023-04-01T00:00:00Z","file_date_updated":"2023-08-16T12:29:06Z","article_processing_charge":"Yes (via OA deal)","oa_version":"Published Version","day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"review","publication":"Current Opinion in Neurobiology","has_accepted_license":"1","article_number":"102695","ec_funded":1,"status":"public","quality_controlled":"1","citation":{"chicago":"Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights from Developing Cerebral Cortex.” <i>Current Opinion in Neurobiology</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.conb.2023.102695\">https://doi.org/10.1016/j.conb.2023.102695</a>.","ieee":"S. Hippenmeyer, “Principles of neural stem cell lineage progression: Insights from developing cerebral cortex,” <i>Current Opinion in Neurobiology</i>, vol. 79, no. 4. Elsevier, 2023.","short":"S. Hippenmeyer, Current Opinion in Neurobiology 79 (2023).","ama":"Hippenmeyer S. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. <i>Current Opinion in Neurobiology</i>. 2023;79(4). doi:<a href=\"https://doi.org/10.1016/j.conb.2023.102695\">10.1016/j.conb.2023.102695</a>","ista":"Hippenmeyer S. 2023. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. Current Opinion in Neurobiology. 79(4), 102695.","apa":"Hippenmeyer, S. (2023). Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. <i>Current Opinion in Neurobiology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.conb.2023.102695\">https://doi.org/10.1016/j.conb.2023.102695</a>","mla":"Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights from Developing Cerebral Cortex.” <i>Current Opinion in Neurobiology</i>, vol. 79, no. 4, 102695, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.conb.2023.102695\">10.1016/j.conb.2023.102695</a>."},"_id":"12679","scopus_import":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"acknowledgement":"I wish to thank all current and past members of the Hippenmeyer laboratory at ISTA for exciting discussions on the subject of this review. I apologize to colleagues whose work I could not cite and/or discuss in the frame of the available space. Work in the Hippenmeyer laboratory on the\r\ndiscussed topic is supported by ISTA institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agree-ment no. 725780 LinPro) to SH.","doi":"10.1016/j.conb.2023.102695","date_updated":"2025-04-15T08:23:06Z","intvolume":"        79","department":[{"_id":"SiHi"}],"date_created":"2023-02-26T12:24:21Z","author":[{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Elsevier","issue":"4","external_id":{"pmid":["36842274"],"isi":["000953497700001"]},"corr_author":"1","isi":1,"publication_status":"published","publication_identifier":{"issn":["0959-4388"]},"title":"Principles of neural stem cell lineage progression: Insights from developing cerebral cortex","keyword":["General Neuroscience"],"month":"04","ddc":["570"],"file":[{"creator":"dernst","checksum":"4d11c4ca87e6cbc4d2ac46d3225ea615","file_id":"14071","file_size":1787894,"date_created":"2023-08-16T12:29:06Z","success":1,"date_updated":"2023-08-16T12:29:06Z","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_name":"2023_CurrentOpinionNeurobio_Hippenmeyer.pdf"}],"project":[{"grant_number":"F7805","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"fulldoi":"https://doi.org/10.1016/j.conb.2023.102695","type":"journal_article","abstract":[{"text":"How to generate a brain of correct size and with appropriate cell-type diversity during development is a major question in Neuroscience. In the developing neocortex, radial glial progenitor (RGP) cells are the main neural stem cells that produce cortical excitatory projection neurons, glial cells, and establish the prospective postnatal stem cell niche in the lateral ventricles. RGPs follow a tightly orchestrated developmental program that when disrupted can result in severe cortical malformations such as microcephaly and megalencephaly. The precise cellular and molecular mechanisms instructing faithful RGP lineage progression are however not well understood. This review will summarize recent conceptual advances that contribute to our understanding of the general principles of RGP lineage progression.","lang":"eng"}],"volume":79},{"editor":[{"first_name":"Wieland","full_name":"Huttner, Wieland","last_name":"Huttner"}],"publication_identifier":{"eisbn":["9781119860914"]},"title":"Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression","publication":"Neocortical Neurogenesis in Development and Evolution","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"08","month":"08","status":"public","quality_controlled":"1","citation":{"mla":"Villalba Requena, Ana, et al. “Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression.” <i>Neocortical Neurogenesis in Development and Evolution</i>, edited by Wieland Huttner, Wiley, 2023, pp. 169–91, doi:<a href=\"https://doi.org/10.1002/9781119860914.ch10\">10.1002/9781119860914.ch10</a>.","ama":"Villalba Requena A, Amberg N, Hippenmeyer S. Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression. In: Huttner W, ed. <i>Neocortical Neurogenesis in Development and Evolution</i>. Wiley; 2023:169-191. doi:<a href=\"https://doi.org/10.1002/9781119860914.ch10\">10.1002/9781119860914.ch10</a>","apa":"Villalba Requena, A., Amberg, N., &#38; Hippenmeyer, S. (2023). Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression. In W. Huttner (Ed.), <i>Neocortical Neurogenesis in Development and Evolution</i> (pp. 169–191). Wiley. <a href=\"https://doi.org/10.1002/9781119860914.ch10\">https://doi.org/10.1002/9781119860914.ch10</a>","ista":"Villalba Requena A, Amberg N, Hippenmeyer S. 2023.Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression. In: Neocortical Neurogenesis in Development and Evolution. , 169–191.","short":"A. Villalba Requena, N. Amberg, S. Hippenmeyer, in:, W. Huttner (Ed.), Neocortical Neurogenesis in Development and Evolution, Wiley, 2023, pp. 169–191.","ieee":"A. Villalba Requena, N. Amberg, and S. Hippenmeyer, “Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression,” in <i>Neocortical Neurogenesis in Development and Evolution</i>, W. Huttner, Ed. Wiley, 2023, pp. 169–191.","chicago":"Villalba Requena, Ana, Nicole Amberg, and Simon Hippenmeyer. “Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression.” In <i>Neocortical Neurogenesis in Development and Evolution</i>, edited by Wieland Huttner, 169–91. Wiley, 2023. <a href=\"https://doi.org/10.1002/9781119860914.ch10\">https://doi.org/10.1002/9781119860914.ch10</a>."},"_id":"14757","scopus_import":"1","fulldoi":"https://doi.org/10.1002/9781119860914.ch10","type":"book_chapter","abstract":[{"lang":"eng","text":"The cerebral cortex is comprised of a vast cell-type diversity sequentially generated by cortical progenitor cells. Faithful progenitor lineage progression requires the tight orchestration of distinct molecular and cellular mechanisms regulating proper progenitor proliferation behavior and differentiation. Correct execution of developmental programs involves a complex interplay of cell intrinsic and tissue-wide mechanisms. Many studies over the past decades have been able to determine a plethora of genes critically involved in cortical development. However, only a few made use of genetic paradigms with sparse and global gene deletion to probe cell-autonomous vs. tissue-wide contribution. In this chapter, we will elaborate on the importance of dissecting the cell-autonomous and tissue-wide mechanisms to gain a precise understanding of gene function during radial glial progenitor lineage progression."}],"doi":"10.1002/9781119860914.ch10","language":[{"iso":"eng"}],"date_updated":"2024-10-09T21:07:46Z","department":[{"_id":"SiHi"}],"year":"2023","date_published":"2023-08-08T00:00:00Z","date_created":"2024-01-08T13:16:36Z","author":[{"full_name":"Villalba Requena, Ana","orcid":"0000-0002-5615-5277","first_name":"Ana","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","last_name":"Villalba Requena"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","last_name":"Amberg"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer"}],"publisher":"Wiley","page":"169-191","corr_author":"1","article_processing_charge":"No","oa_version":"None","publication_status":"published"},{"file_date_updated":"2024-01-16T09:26:52Z","oa_version":"Published Version","article_processing_charge":"Yes","oa":1,"year":"2023","date_published":"2023-04-11T00:00:00Z","language":[{"iso":"eng"}],"pmid":1,"quality_controlled":"1","status":"public","_id":"14783","citation":{"short":"G.T. Cheung, O. Chever, A. Rollenhagen, N. Quenech’du, P. Ezan, J.H.R. Lübke, N. Rouach, Cells 12 (2023).","chicago":"Cheung, Giselle T, Oana Chever, Astrid Rollenhagen, Nicole Quenech’du, Pascal Ezan, Joachim H. R. Lübke, and Nathalie Rouach. “Astroglial Connexin 43 Regulates Synaptic Vesicle Release at Hippocampal Synapses.” <i>Cells</i>. MDPI, 2023. <a href=\"https://doi.org/10.3390/cells12081133\">https://doi.org/10.3390/cells12081133</a>.","ieee":"G. T. Cheung <i>et al.</i>, “Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses,” <i>Cells</i>, vol. 12, no. 8. MDPI, 2023.","mla":"Cheung, Giselle T., et al. “Astroglial Connexin 43 Regulates Synaptic Vesicle Release at Hippocampal Synapses.” <i>Cells</i>, vol. 12, no. 8, 1133, MDPI, 2023, doi:<a href=\"https://doi.org/10.3390/cells12081133\">10.3390/cells12081133</a>.","apa":"Cheung, G. T., Chever, O., Rollenhagen, A., Quenech’du, N., Ezan, P., Lübke, J. H. R., &#38; Rouach, N. (2023). Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses. <i>Cells</i>. MDPI. <a href=\"https://doi.org/10.3390/cells12081133\">https://doi.org/10.3390/cells12081133</a>","ista":"Cheung GT, Chever O, Rollenhagen A, Quenech’du N, Ezan P, Lübke JHR, Rouach N. 2023. Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses. Cells. 12(8), 1133.","ama":"Cheung GT, Chever O, Rollenhagen A, et al. Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses. <i>Cells</i>. 2023;12(8). doi:<a href=\"https://doi.org/10.3390/cells12081133\">10.3390/cells12081133</a>"},"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publication":"Cells","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","day":"11","article_number":"1133","has_accepted_license":"1","external_id":{"pmid":["37190042"],"isi":["000977445700001"]},"issue":"8","isi":1,"publication_status":"published","acknowledgement":"This research was funded by grants from the European Research Council (Consolidator grant #683154) and European Union’s Horizon 2020 research and innovation program (Marie Sklodowska-Curie Innovative Training Networks, grant #722053, EU-GliaPhD) to N.R., as well as from FP7-PEOPLE Marie Curie Intra-European Fellowship for career development (grant #622289) to G.C. We thank Elena Dossi, Grégory Ghézali, and Jérémie Teillon for support with setting up the MEA system for the two-photon microscope. We would also like to thank Tayfun Palaz for their technical assistance with the EM preparations.","doi":"10.3390/cells12081133","date_created":"2024-01-10T09:46:35Z","author":[{"last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T","full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572"},{"full_name":"Chever, Oana","first_name":"Oana","last_name":"Chever"},{"first_name":"Astrid","full_name":"Rollenhagen, Astrid","last_name":"Rollenhagen"},{"full_name":"Quenech’du, Nicole","first_name":"Nicole","last_name":"Quenech’du"},{"last_name":"Ezan","first_name":"Pascal","full_name":"Ezan, Pascal"},{"full_name":"Lübke, Joachim H. R.","first_name":"Joachim H. R.","last_name":"Lübke"},{"last_name":"Rouach","first_name":"Nathalie","full_name":"Rouach, Nathalie"}],"date_updated":"2024-01-16T09:29:35Z","department":[{"_id":"SiHi"}],"intvolume":"        12","publisher":"MDPI","file":[{"creator":"dernst","checksum":"6798cd75d8857976fbc58a43fd173d68","file_id":"14808","file_size":7931643,"date_updated":"2024-01-16T09:26:52Z","content_type":"application/pdf","date_created":"2024-01-16T09:26:52Z","success":1,"access_level":"open_access","relation":"main_file","file_name":"2023_Cells_Cheung.pdf"}],"volume":12,"abstract":[{"lang":"eng","text":"Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic astroglial processes and plays major roles in synaptic transmission. We have previously found that astroglial Cx43 controls synaptic glutamate levels and allows for activity-dependent glutamine release to sustain physiological synaptic transmissions and cognitiogns. However, whether Cx43 is important for the release of synaptic vesicles, which is a critical component of synaptic efficacy, remains unanswered. Here, using transgenic mice with a glial conditional knockout of Cx43 (Cx43−/−), we investigate whether and how astrocytes regulate the release of synaptic vesicles from hippocampal synapses. We report that CA1 pyramidal neurons and their synapses develop normally in the absence of astroglial Cx43. However, a significant impairment in synaptic vesicle distribution and release dynamics were observed. In particular, the FM1-43 assays performed using two-photon live imaging and combined with multi-electrode array stimulation in acute hippocampal slices, revealed a slower rate of synaptic vesicle release in Cx43−/− mice. Furthermore, paired-pulse recordings showed that synaptic vesicle release probability was also reduced and is dependent on glutamine supply via Cx43 hemichannel (HC). Taken together, we have uncovered a role for Cx43 in regulating presynaptic functions by controlling the rate and probability of synaptic vesicle release. Our findings further highlight the significance of astroglial Cx43 in synaptic transmission and efficacy."}],"type":"journal_article","fulldoi":"https://doi.org/10.3390/cells12081133","publication_identifier":{"issn":["2073-4409"]},"month":"04","keyword":["General Medicine"],"title":"Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses","ddc":["570"]},{"article_processing_charge":"Yes (via OA deal)","oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"file_date_updated":"2023-05-02T09:26:21Z","pmid":1,"language":[{"iso":"eng"}],"year":"2023","date_published":"2023-04-27T00:00:00Z","oa":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","citation":{"apa":"Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz, L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal excitability and survival. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">https://doi.org/10.1016/j.cell.2023.02.037</a>","ista":"Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.","ama":"Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. <i>Cell</i>. 2023;186(9):1950-1967.e25. doi:<a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">10.1016/j.cell.2023.02.037</a>","mla":"Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25, doi:<a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">10.1016/j.cell.2023.02.037</a>.","chicago":"Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova, Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">https://doi.org/10.1016/j.cell.2023.02.037</a>.","ieee":"L. Knaus <i>et al.</i>, “Large neutral amino acid levels tune perinatal neuronal excitability and survival,” <i>Cell</i>, vol. 186, no. 9. Elsevier, p. 1950–1967.e25, 2023.","short":"L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A. Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N. Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25."},"_id":"12802","status":"public","quality_controlled":"1","has_accepted_license":"1","ec_funded":1,"day":"27","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","publication":"Cell","publication_status":"published","isi":1,"issue":"9","external_id":{"isi":["000991468700001"],"pmid":["36996814"]},"corr_author":"1","publisher":"Elsevier","page":"1950-1967.e25","intvolume":"       186","date_updated":"2026-11-11T23:30:14Z","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"date_created":"2023-04-05T08:15:40Z","author":[{"first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","last_name":"Knaus"},{"orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette","last_name":"Basilico"},{"first_name":"Daniel","full_name":"Malzl, Daniel","last_name":"Malzl"},{"first_name":"Maria","full_name":"Gerykova Bujalkova, Maria","last_name":"Gerykova Bujalkova"},{"last_name":"Smogavec","first_name":"Mateja","full_name":"Smogavec, Mateja"},{"first_name":"Lena A.","full_name":"Schwarz, Lena A.","last_name":"Schwarz"},{"first_name":"Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","full_name":"Gorkiewicz, Sarah","last_name":"Gorkiewicz"},{"last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","last_name":"Pauler"},{"last_name":"Knittl-Frank","full_name":"Knittl-Frank, Christian","first_name":"Christian"},{"last_name":"Tassinari","full_name":"Tassinari, Marianna","id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e","first_name":"Marianna"},{"last_name":"Maulide","full_name":"Maulide, Nuno","first_name":"Nuno"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"last_name":"Menche","first_name":"Jörg","full_name":"Menche, Jörg"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"}],"doi":"10.1016/j.cell.2023.02.037","acknowledgement":"We thank A. Freeman and V. Voronin for technical assistance, S. Deixler, A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal colony. We thank L. Andersen and J. Sonntag, who were involved in generating the MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance with the proteomic analysis, as well as the ISTA electron microscopy and Imaging and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated using Biorender.com. This work was supported by the Austrian Science Fund (FWF, DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.","type":"journal_article","fulldoi":"https://doi.org/10.1016/j.cell.2023.02.037","volume":186,"abstract":[{"lang":"eng","text":"Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction."}],"file":[{"file_name":"2023_Cell_Knaus.pdf","relation":"main_file","access_level":"open_access","date_created":"2023-05-02T09:26:21Z","success":1,"date_updated":"2023-05-02T09:26:21Z","content_type":"application/pdf","file_size":15712841,"file_id":"12889","checksum":"47e94fbe19e86505b429cb7a5b503ce6","creator":"dernst"}],"project":[{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232","name":"Molecular Drug Targets"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"ddc":["570"],"title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","keyword":["General Biochemistry","Genetics and Molecular Biology"],"month":"04","related_material":{"record":[{"id":"13107","status":"public","relation":"dissertation_contains"},{"relation":"dissertation_contains","id":"19557","status":"public"}],"link":[{"url":"https://ista.ac.at/en/news/feed-them-or-lose-them/","description":"News on ISTA Website","relation":"press_release"}]},"publication_identifier":{"issn":["0092-8674"]}},{"has_accepted_license":"1","article_number":"abq1263","ec_funded":1,"publication":"Science Advances","day":"01","article_type":"original","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","citation":{"short":"N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).","ieee":"N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression,” <i>Science Advances</i>, vol. 8, no. 44. American Association for the Advancement of Science, 2022.","chicago":"Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” <i>Science Advances</i>. American Association for the Advancement of Science, 2022. <a href=\"https://doi.org/10.1126/sciadv.abq1263\">https://doi.org/10.1126/sciadv.abq1263</a>.","mla":"Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” <i>Science Advances</i>, vol. 8, no. 44, abq1263, American Association for the Advancement of Science, 2022, doi:<a href=\"https://doi.org/10.1126/sciadv.abq1263\">10.1126/sciadv.abq1263</a>.","apa":"Amberg, N., Pauler, F., Streicher, C., &#38; Hippenmeyer, S. (2022). Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.abq1263\">https://doi.org/10.1126/sciadv.abq1263</a>","ista":"Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. 8(44), abq1263.","ama":"Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. <i>Science Advances</i>. 2022;8(44). doi:<a href=\"https://doi.org/10.1126/sciadv.abq1263\">10.1126/sciadv.abq1263</a>"},"_id":"11336","status":"public","quality_controlled":"1","language":[{"iso":"eng"}],"pmid":1,"year":"2022","date_published":"2022-11-01T00:00:00Z","oa":1,"article_processing_charge":"No","oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"file_date_updated":"2023-03-21T14:18:10Z","ddc":["570"],"title":"Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression","month":"11","related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/"}]},"publication_identifier":{"issn":["2375-2548"]},"type":"journal_article","fulldoi":"https://doi.org/10.1126/sciadv.abq1263","volume":8,"abstract":[{"text":"The generation of a correctly-sized cerebral cortex with all-embracing neuronal and glial cell-type diversity critically depends on faithful radial glial progenitor (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene expression instructs RGP lineage progression is unknown. Here we utilize Mosaic Analysis with Double Markers (MADM)-based single cell technology and demonstrate that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts at the global tissue-wide level. Conversely, cortical astrocyte production and maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation. We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression that are dependent on complex interplays between intrinsic and tissue-wide properties. In a broader context our results imply a critical role for the genetic and cellular niche environment in neural stem cell behavior.","lang":"eng"}],"file":[{"file_name":"sciadv.abq1263.pdf","relation":"main_file","access_level":"open_access","content_type":"application/pdf","date_updated":"2023-03-21T14:18:10Z","date_created":"2023-03-21T14:18:10Z","success":1,"file_size":2973998,"file_id":"12742","checksum":"0117023e188542082ca6693cf39e7f03","creator":"patrickd"}],"project":[{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"},{"_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression","grant_number":"T01031"}],"publisher":"American Association for the Advancement of Science","date_updated":"2025-09-09T14:30:38Z","intvolume":"         8","department":[{"_id":"SiHi"}],"date_created":"2022-04-26T15:04:50Z","author":[{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg"},{"last_name":"Pauler","first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"doi":"10.1126/sciadv.abq1263","acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS  Unit)  and  S.  Gharagozlou  for  technical  support.  This  research  was  supported  by  the  Scientific  Service  Units  (SSU)  of  IST  Austria  through  resources  provided  by  the  Imaging  &  Optics Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A. received funding   from   the   FWF   Firnberg-Programm   (T   1031).   The   work   was   supported   by   IST   institutional  funds  and  by  the  European  Research  Council  (ERC)  under  the  European  Union’s  Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","publication_status":"published","isi":1,"issue":"44","corr_author":"1","external_id":{"pmid":["36322669"],"isi":["000918406800019"]}},{"project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"},{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425"}],"abstract":[{"text":"Mutations are acquired frequently, such that each cell's genome inscribes its history of cell divisions. Common genomic alterations involve loss of heterozygosity (LOH). LOH accumulates throughout the genome, offering large encoding capacity for inferring cell lineage. Using only single-cell RNA sequencing (scRNA-seq) of mouse brain cells, we found that LOH events spanning multiple genes are revealed as tracts of monoallelically expressed, constitutionally heterozygous single-nucleotide variants (SNVs). We simultaneously inferred cell lineage and marked developmental time points based on X chromosome inactivation and the total number of LOH events while identifying cell types from gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. This type of retrospective analysis could be incorporated into scRNA-seq pipelines and, compared with experimental approaches for determining lineage in model organisms, is applicable where genetic engineering is prohibited, such as humans.","lang":"eng"}],"volume":13,"type":"journal_article","fulldoi":"https://doi.org/10.1016/j.cels.2022.03.006","month":"06","title":"Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development","publication_identifier":{"eissn":["2405-4720"],"issn":["2405-4712"]},"ddc":["570"],"external_id":{"pmid":["35452605"],"isi":["000814124400002"]},"issue":"6","publication_status":"published","isi":1,"doi":"10.1016/j.cels.2022.03.006","acknowledgement":"D.J.A. thanks Wayne K. Potts, Alan R. Rogers, Kristen Hawkes, Ryk Ward, and Jon Seger for inspiring a young undergraduate to apply evolutionary theory to intraorganism development. Supported by the Paul G. Allen Frontiers Group (University of Washington); NIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program 725780 LinPro to S.H.","main_file_link":[{"url":"https://doi.org/10.1016/j.cels.2022.03.006","open_access":"1"}],"page":"438-453.e5","publisher":"Elsevier","author":[{"last_name":"Anderson","full_name":"Anderson, Donovan J.","first_name":"Donovan J."},{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","last_name":"Pauler"},{"full_name":"Mckenna, Aaron","first_name":"Aaron","last_name":"Mckenna"},{"full_name":"Shendure, Jay","first_name":"Jay","last_name":"Shendure"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Marshall S.","full_name":"Horwitz, Marshall S.","last_name":"Horwitz"}],"date_created":"2022-06-19T22:01:57Z","department":[{"_id":"SiHi"}],"intvolume":"        13","date_updated":"2026-06-18T17:15:22Z","_id":"11449","citation":{"ama":"Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. <i>Cell Systems</i>. 2022;13(6):438-453.e5. doi:<a href=\"https://doi.org/10.1016/j.cels.2022.03.006\">10.1016/j.cels.2022.03.006</a>","ista":"Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. 2022. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. 13(6), 438–453.e5.","apa":"Anderson, D. J., Pauler, F., Mckenna, A., Shendure, J., Hippenmeyer, S., &#38; Horwitz, M. S. (2022). Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. <i>Cell Systems</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cels.2022.03.006\">https://doi.org/10.1016/j.cels.2022.03.006</a>","mla":"Anderson, Donovan J., et al. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” <i>Cell Systems</i>, vol. 13, no. 6, Elsevier, 2022, p. 438–453.e5, doi:<a href=\"https://doi.org/10.1016/j.cels.2022.03.006\">10.1016/j.cels.2022.03.006</a>.","ieee":"D. J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, and M. S. Horwitz, “Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development,” <i>Cell Systems</i>, vol. 13, no. 6. Elsevier, p. 438–453.e5, 2022.","chicago":"Anderson, Donovan J., Florian Pauler, Aaron Mckenna, Jay Shendure, Simon Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” <i>Cell Systems</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.cels.2022.03.006\">https://doi.org/10.1016/j.cels.2022.03.006</a>.","short":"D.J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, Cell Systems 13 (2022) 438–453.e5."},"quality_controlled":"1","status":"public","scopus_import":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Cell Systems","day":"15","article_type":"original","ec_funded":1,"oa_version":"Published Version","article_processing_charge":"No","oa":1,"date_published":"2022-06-15T00:00:00Z","year":"2022","language":[{"iso":"eng"}],"pmid":1},{"file":[{"creator":"dernst","file_size":7552298,"file_id":"11461","checksum":"525d2618e855139089bbfc3e3d49d1b2","access_level":"open_access","date_created":"2022-06-24T08:22:59Z","success":1,"content_type":"application/pdf","date_updated":"2022-06-24T08:22:59Z","file_name":"2022_MolecularAutism_Schaaf.pdf","relation":"main_file"}],"volume":13,"abstract":[{"text":"Background: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology.\r\nMethods: Here, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques.\r\nResults: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages.\r\nLimitations: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation.\r\nConclusions: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life.","lang":"eng"}],"fulldoi":"https://doi.org/10.1186/s13229-022-00508-3","type":"journal_article","month":"06","keyword":["Psychiatry and Mental health","Developmental Biology","Developmental Neuroscience","Molecular Biology"],"title":"WDFY3 mutation alters laminar position and morphology of cortical neurons","publication_identifier":{"issn":["2040-2392"]},"related_material":{"link":[{"url":"https://doi.org/10.1186/s13229-023-00539-4","relation":"erratum"}]},"ddc":["570"],"external_id":{"isi":["000814641400001"],"pmid":["35733184"]},"publication_status":"published","isi":1,"doi":"10.1186/s13229-022-00508-3","acknowledgement":"This study was funded by NIMH R21MH115347 to KSZ. KSZ is further supported by Shriners Hospitals for Children.\r\nWe would like to thank Angelo Harlan de Crescenzo for early contributions to this project.","publisher":"Springer Nature","author":[{"first_name":"Zachary A.","full_name":"Schaaf, Zachary A.","last_name":"Schaaf"},{"full_name":"Tat, Lyvin","first_name":"Lyvin","last_name":"Tat"},{"last_name":"Cannizzaro","first_name":"Noemi","full_name":"Cannizzaro, Noemi"},{"full_name":"Green, Ralph","first_name":"Ralph","last_name":"Green"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer"},{"first_name":"Konstantinos S.","full_name":"Zarbalis, Konstantinos S.","last_name":"Zarbalis"}],"date_created":"2022-06-23T14:28:55Z","date_updated":"2025-06-11T13:34:57Z","intvolume":"        13","department":[{"_id":"SiHi"}],"_id":"11460","citation":{"mla":"Schaaf, Zachary A., et al. “WDFY3 Mutation Alters Laminar Position and Morphology of Cortical Neurons.” <i>Molecular Autism</i>, vol. 13, 27, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1186/s13229-022-00508-3\">10.1186/s13229-022-00508-3</a>.","apa":"Schaaf, Z. A., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S., &#38; Zarbalis, K. S. (2022). WDFY3 mutation alters laminar position and morphology of cortical neurons. <i>Molecular Autism</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13229-022-00508-3\">https://doi.org/10.1186/s13229-022-00508-3</a>","ista":"Schaaf ZA, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis KS. 2022. WDFY3 mutation alters laminar position and morphology of cortical neurons. Molecular Autism. 13, 27.","ama":"Schaaf ZA, Tat L, Cannizzaro N, et al. WDFY3 mutation alters laminar position and morphology of cortical neurons. <i>Molecular Autism</i>. 2022;13. doi:<a href=\"https://doi.org/10.1186/s13229-022-00508-3\">10.1186/s13229-022-00508-3</a>","short":"Z.A. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K.S. Zarbalis, Molecular Autism 13 (2022).","ieee":"Z. A. Schaaf <i>et al.</i>, “WDFY3 mutation alters laminar position and morphology of cortical neurons,” <i>Molecular Autism</i>, vol. 13. Springer Nature, 2022.","chicago":"Schaaf, Zachary A., Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke, Simon Hippenmeyer, and Konstantinos S. Zarbalis. “WDFY3 Mutation Alters Laminar Position and Morphology of Cortical Neurons.” <i>Molecular Autism</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1186/s13229-022-00508-3\">https://doi.org/10.1186/s13229-022-00508-3</a>."},"quality_controlled":"1","status":"public","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","publication":"Molecular Autism","day":"22","article_number":"27","has_accepted_license":"1","file_date_updated":"2022-06-24T08:22:59Z","oa_version":"Published Version","article_processing_charge":"No","oa":1,"year":"2022","date_published":"2022-06-22T00:00:00Z","pmid":1,"language":[{"iso":"eng"}]}]