[{"department":[{"_id":"SiHi"},{"_id":"LoSw"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"project":[{"_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","name":"Development and Evolution of Tetrapod Motor Circuits","grant_number":"101041551"},{"_id":"8da85f50-16d5-11f0-9cad-eab8b0ff6c9e","name":"Stem Cell Modulation in Neural Development and Regeneration/ P14-Swim-to-limb transition: cell type to connection diversity","grant_number":"F7814"},{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"citation":{"ista":"Gobeil SA, Da Silveira Neto F, Silvestrelli G, Smits MG, Streicher C, Cheung GT, Hippenmeyer S, Sweeney LB. Lineage origin of spinal cord cell type diversity. bioRxiv, <a href=\"https://doi.org/10.64898/2026.02.12.705305\">10.64898/2026.02.12.705305</a>.","ieee":"S. A. Gobeil <i>et al.</i>, “Lineage origin of spinal cord cell type diversity,” <i>bioRxiv</i>. .","short":"S.A. Gobeil, F. Da Silveira Neto, G. Silvestrelli, M.G. Smits, C. Streicher, G.T. Cheung, S. Hippenmeyer, L.B. Sweeney, BioRxiv (n.d.).","apa":"Gobeil, S. A., Da Silveira Neto, F., Silvestrelli, G., Smits, M. G., Streicher, C., Cheung, G. T., … Sweeney, L. B. (n.d.). Lineage origin of spinal cord cell type diversity. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.02.12.705305\">https://doi.org/10.64898/2026.02.12.705305</a>","mla":"Gobeil, Sophie A., et al. “Lineage Origin of Spinal Cord Cell Type Diversity.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.64898/2026.02.12.705305\">10.64898/2026.02.12.705305</a>.","ama":"Gobeil SA, Da Silveira Neto F, Silvestrelli G, et al. Lineage origin of spinal cord cell type diversity. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.64898/2026.02.12.705305\">10.64898/2026.02.12.705305</a>","chicago":"Gobeil, Sophie A, Francisco Da Silveira Neto, Giulia Silvestrelli, Matthijs Geert Smits, Carmen Streicher, Giselle T Cheung, Simon Hippenmeyer, and Lora B. Sweeney. “Lineage Origin of Spinal Cord Cell Type Diversity.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.64898/2026.02.12.705305\">https://doi.org/10.64898/2026.02.12.705305</a>."},"type":"preprint","_id":"21291","oa_version":"Preprint","title":"Lineage origin of spinal cord cell type diversity","publication_status":"submitted","date_updated":"2026-04-14T08:16:55Z","month":"02","date_published":"2026-02-16T00:00:00Z","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"article_processing_charge":"No","oa":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","author":[{"first_name":"Sophie A","last_name":"Gobeil","id":"2f3e9efb-eb24-11ec-86b2-88efb11d59fa","full_name":"Gobeil, Sophie A"},{"full_name":"Da Silveira Neto, Francisco","id":"8cfb7412-10a7-11f1-add1-82b44e6418f2","last_name":"Da Silveira Neto","first_name":"Francisco"},{"last_name":"Silvestrelli","id":"12632ae8-799e-11ef-94a2-e5a3b5ef49e9","full_name":"Silvestrelli, Giulia","first_name":"Giulia"},{"last_name":"Smits","id":"7a231d52-e216-11ee-a0bb-8acd55f8f1f0","full_name":"Smits, Matthijs Geert","first_name":"Matthijs Geert"},{"last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","first_name":"Carmen"},{"full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","last_name":"Cheung","orcid":"0000-0001-8457-2572","first_name":"Giselle T"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"},{"first_name":"Lora Beatrice Jaeger","orcid":"0000-0001-9242-5601","last_name":"Sweeney","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","full_name":"Sweeney, Lora Beatrice Jaeger"}],"ddc":["570"],"OA_place":"repository","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"The complexity and specificity of movement in vertebrates is driven by a rich diversity of spinal motor and interneuron cell types. During development, eleven spinal cord progenitor domains generate an equivalent number of cardinal neuron types. How progenitor domains, individual progenitors, and post-mitotic diversity relate is still unknown. We performed high-resolution, single-progenitor cell lineage tracing in the embryonic mouse spinal cord using mosaic analysis with double markers (MADM). Our quantitative study of lineage progression revealed that spinal cord progenitors undergo highly variable numbers of proliferative, neurogenic, and gliogenic cell divisions. The nascent clonally-related neurons migrate radially over large distances, span the dorsoventral axis, and even cross the midline, demonstrating striking bilaterality. Molecular and morphometric analysis indicate high levels of progenitor multipotency, with an individual progenitor capable of producing several molecularly and morphologically distinct neuron types, as well as astrocytes. These findings redefine spinal cord development as a process in which lineage variability — rather than rigid progenitor identity — drives the generation of cellular diversity.","lang":"eng"}],"doi":"10.64898/2026.02.12.705305","corr_author":"1","publication":"bioRxiv","date_created":"2026-02-17T11:36:20Z","acknowledgement":"We would like to thank Elizabeth Marin, Anna Kicheva, Igor Adameyko, and James Briscoe as\r\nwell as members of the Sweeney and Hippemeyer labs and SFB consortium for comments on\r\nthe manuscript. We are also grateful for the technical support of the Preclinical and Imaging and\r\nOptics Facilities support teams (ISTA). In addition, we thank our funding sources for providing\r\nthe resources to do these experiments: Horizon Europe ERC Starting Grant Number 101041551\r\n(M.S.; L.B.S.); Special Research Program (SFB) of the Austrian Science Fund (FWF)\r\nNeuroStem Modulation Project numbers F7814-B (S.A.G.; M.S.; G.S.; and L.B.S.) and F7805\r\n(G.C. and S.H.). S.A.G is supported by a Boehringer Ingelheim Fonds PhD Fellowship, F.D.S.N.\r\nby an Institute of Science and Technology Austria (ISTA) GROW fellowship, and G.C. by an\r\nISTA Plus postdoctoral fellowship from the European Commission. S.H./L.B.S. and G.C. were\r\nadditionally supported by institutional funds from the ISTA and the University of Exeter,\r\nrespectively. ","main_file_link":[{"open_access":"1","url":"https://doi.org/10.64898/2026.02.12.705305"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"status":"public","OA_type":"green","day":"16","year":"2026"},{"department":[{"_id":"SiHi"}],"citation":{"ista":"Villalba Requena A, Beattie RJ, Pauler F, Streicher C, Miranda O, Krausgruber T, Senekowitsch M, Farlik M, Bock C, Rülicke T, Hippenmeyer S. Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner. bioRxiv, <a href=\"https://doi.org/10.64898/2026.05.01.722172\">10.64898/2026.05.01.722172</a>.","ieee":"A. Villalba Requena <i>et al.</i>, “Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner,” <i>bioRxiv</i>. .","short":"A. Villalba Requena, R.J. Beattie, F. Pauler, C. Streicher, O. Miranda, T. Krausgruber, M. Senekowitsch, M. Farlik, C. Bock, T. Rülicke, S. Hippenmeyer, BioRxiv (n.d.).","apa":"Villalba Requena, A., Beattie, R. J., Pauler, F., Streicher, C., Miranda, O., Krausgruber, T., … Hippenmeyer, S. (n.d.). Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.05.01.722172\">https://doi.org/10.64898/2026.05.01.722172</a>","mla":"Villalba Requena, Ana, et al. “Mtor/Rptor Function Globally Prevents Cortical Microcephaly and Cell-Autonomously Promotes Postnatal Neuron Survival in Cell Type Specific Manner.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.64898/2026.05.01.722172\">10.64898/2026.05.01.722172</a>.","chicago":"Villalba Requena, Ana, Robert J Beattie, Florian Pauler, Carmen Streicher, Osvaldo Miranda, Thomas Krausgruber, Martin Senekowitsch, et al. “Mtor/Rptor Function Globally Prevents Cortical Microcephaly and Cell-Autonomously Promotes Postnatal Neuron Survival in Cell Type Specific Manner.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.64898/2026.05.01.722172\">https://doi.org/10.64898/2026.05.01.722172</a>.","ama":"Villalba Requena A, Beattie RJ, Pauler F, et al. Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.64898/2026.05.01.722172\">10.64898/2026.05.01.722172</a>"},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"MassSpec"},{"_id":"Bio"}],"project":[{"call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex","grant_number":"M02416"},{"grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"oa_version":"Preprint","title":"Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner","type":"preprint","_id":"21962","date_published":"2026-05-05T00:00:00Z","date_updated":"2026-06-16T08:45:25Z","month":"05","publication_status":"submitted","oa":1,"license":"https://creativecommons.org/licenses/by-nc/4.0/","author":[{"last_name":"Villalba Requena","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","full_name":"Villalba Requena, Ana","first_name":"Ana","orcid":"0000-0002-5615-5277"},{"first_name":"Robert J","orcid":"0000-0002-8483-8753","last_name":"Beattie","full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-7462-0048","first_name":"Florian","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler"},{"full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen"},{"first_name":"Osvaldo","orcid":"0000-0001-6618-6889","last_name":"Miranda","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","full_name":"Miranda, Osvaldo"},{"first_name":"Thomas","last_name":"Krausgruber","full_name":"Krausgruber, Thomas"},{"first_name":"Martin","last_name":"Senekowitsch","full_name":"Senekowitsch, Martin"},{"first_name":"Matthias","full_name":"Farlik, Matthias","last_name":"Farlik"},{"first_name":"Christoph","last_name":"Bock","full_name":"Bock, Christoph"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"article_processing_charge":"No","abstract":[{"text":"The generation of faithful cell-type diversity and correct projection neuron numbers is essential for cerebral cortex development. Corticogenesis is however susceptible to genetic interference of critical signaling pathways, including mutations in Mtor/Rptor that lead to microcephaly. How the loss of Rptor/mTORC1 function affects cortical developmental programs, at single cell level, is still unknown. Here, we utilized Mosaic Analysis with Double Markers (MADM) technology to probe Rptor gene function upon sparse single cell- or global tissue-wide ablation. We found that tissue-wide effects drive the etiology of cortical microcephaly upon loss of Rptor, rather than deficits in projection neuron genesis. Conversely, Rptor function is cell-autonomously required for postnatal projection neuron survival in a highly cell-type-specific manner. Collectively, our results suggest that the fine balance of precise cell-type-specific cell-autonomous Rptor/mTORC1 function in concert with non-cell-autonomous tissue-wide effects is essential for the development of a properly-sized cerebral cortex with accurate projection neuron diversity.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"OA_place":"repository","has_accepted_license":"1","main_file_link":[{"url":"https://doi.org/10.64898/2026.05.01.722172","open_access":"1"}],"language":[{"iso":"eng"}],"doi":"10.64898/2026.05.01.722172","acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer (VBCF GmbH, NGS Unit), and A.\r\nNicolas (IST Austria Lab Support Facility / Mass Spectrometry Facility) for technical support; K. Ferencak,\r\nI. Aykara, P. Hirschfeld, E. Fisher, S. Laukoter, L. Andersen for initial experiments and/or assistance; and\r\nall members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service\r\nUnits (SSU) of IST Austria through resources provided by the Imaging and Optics- (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF). R.B. received support from FWF Meitner-Programm (M 2416). This\r\nwork was also supported by IST Austria institutional funds; the People Programme (Marie Curie Actions)\r\nof the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement\r\nNo 618444 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020\r\nresearch and innovation programme (grant agreement No 725780 LinPro) to S.H.","publication":"bioRxiv","date_created":"2026-06-09T08:08:18Z","year":"2026","status":"public","OA_type":"green","day":"05","ec_funded":1},{"OA_type":"green","day":"05","ec_funded":1,"status":"public","year":"2026","acknowledgement":"We thank Kay-Uwe Wagner (Wayne State University) for generously sharing Jak1/2–flox mouse lines; A.\r\nSommer (VBCF GmbH, NGS Unit) for technical support; N. Kim, V. Mick, S. Schnabl, S. Gobeil, and L.\r\nAndersen for technical assistance; all members of the Hippenmeyer lab for discussion and B. Novitch for\r\ncomments on earlier versions of the manuscript. This research was supported by the Scientific Service Units\r\n(SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF). O.A.M received support from the Austrian Academy of Sciences\r\nÖAW (DOC 186584), and N.A. from FWF Elise Richter Program (Grant V1041T). This work was also\r\nsupported by IST Austria institutional funds; FWF SFB F78 (Neuro Stem Modulation) to S.H., and the\r\nEuropean Research Council (ERC) under the European Union’s Horizon 2020 research and innovation\r\nprogramme (grant agreement No 725780 LinPro) to S.H.","corr_author":"1","publication":"bioRxiv","date_created":"2026-06-09T08:08:53Z","doi":"10.64898/2026.05.01.722191","language":[{"iso":"eng"}],"has_accepted_license":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.64898/2026.05.01.722191"}],"OA_place":"repository","ddc":["570"],"abstract":[{"text":"The cerebral cortex consists of immense numbers of neuronal and glial cell-types derived from radial glial progenitor (RGP) cells. How RGPs generate appropriate quantities of distinct cortical cell-types to safeguard a brain of correct size, is not well understood. However, genetic aberration in human, including mutations in PTEN, lead to cortical malformation such as macrocephaly, albeit with unknown etiology. Here we utilized Mosaic Analysis with Double Markers (MADM)-based clonal analysis and single cell phenotyping to decipher the role of Pten in neurogenic and gliogenic RGP lineage progression during cortical ontogeny. While neurogenic RGP lineage progression and projection neuron production was moderately altered in the absence of Pten, cortical astrocyte production was drastically increased. Through genetic epistasis experiments we show that the loss of Pten uncouples astrocyte generation from essential growth factor signaling hubs, funneling into MAPK. Collectively, our results suggest that Pten regulates RGP lineage progression with distinct sequential functions in cortical projection neurogenesis and astrocyte production to ensure the emergence of a correctly-sized cerebral cortex.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"author":[{"last_name":"Miranda","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","full_name":"Miranda, Osvaldo","first_name":"Osvaldo","orcid":"0000-0001-6618-6889"},{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","last_name":"Contreras","first_name":"Ximena"},{"full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","orcid":"0000-0002-7462-0048","first_name":"Florian"},{"first_name":"Amarbayasgalan","last_name":"Davaatseren","full_name":"Davaatseren, Amarbayasgalan","id":"70ADC922-B424-11E9-99E3-BA18E6697425"},{"last_name":"Amberg","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","orcid":"0000-0002-3183-8207"},{"first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher"},{"last_name":"Villalba Requena","full_name":"Villalba Requena, Ana","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","first_name":"Ana","orcid":"0000-0002-5615-5277"},{"last_name":"Heger","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena"},{"full_name":"Marie, Corentine","last_name":"Marie","first_name":"Corentine"},{"first_name":"Bassem A.","full_name":"Hassan, Bassem A.","last_name":"Hassan"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"month":"05","date_updated":"2026-06-16T08:57:20Z","publication_status":"submitted","date_published":"2026-05-05T00:00:00Z","_id":"21963","type":"preprint","title":"Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production","oa_version":"Preprint","project":[{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"citation":{"ieee":"O. Miranda <i>et al.</i>, “Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production,” <i>bioRxiv</i>. .","ista":"Miranda O, Contreras X, Pauler F, Davaatseren A, Amberg N, Streicher C, Villalba Requena A, Heger A-M, Marie C, Hassan BA, Rülicke T, Hippenmeyer S. Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production. bioRxiv, <a href=\"https://doi.org/10.64898/2026.05.01.722191\">10.64898/2026.05.01.722191</a>.","short":"O. Miranda, X. Contreras, F. Pauler, A. Davaatseren, N. Amberg, C. Streicher, A. Villalba Requena, A.-M. Heger, C. Marie, B.A. Hassan, T. Rülicke, S. Hippenmeyer, BioRxiv (n.d.).","mla":"Miranda, Osvaldo, et al. “Pten Orchestrates Neurogenic Radial Glia Lineage Progression and Tunes Neocortical Astrocyte Production.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.64898/2026.05.01.722191\">10.64898/2026.05.01.722191</a>.","apa":"Miranda, O., Contreras, X., Pauler, F., Davaatseren, A., Amberg, N., Streicher, C., … Hippenmeyer, S. (n.d.). Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.05.01.722191\">https://doi.org/10.64898/2026.05.01.722191</a>","chicago":"Miranda, Osvaldo, Ximena Contreras, Florian Pauler, Amarbayasgalan Davaatseren, Nicole Amberg, Carmen Streicher, Ana Villalba Requena, et al. “Pten Orchestrates Neurogenic Radial Glia Lineage Progression and Tunes Neocortical Astrocyte Production.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.64898/2026.05.01.722191\">https://doi.org/10.64898/2026.05.01.722191</a>.","ama":"Miranda O, Contreras X, Pauler F, et al. Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.64898/2026.05.01.722191\">10.64898/2026.05.01.722191</a>"},"department":[{"_id":"SiHi"},{"_id":"PreCl"},{"_id":"GradSch"}]},{"oa_version":"Preprint","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.05.22.655488"}],"language":[{"iso":"eng"}],"title":"Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development","doi":"10.1101/2025.05.22.655488","type":"preprint","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).","_id":"19762","date_created":"2025-05-29T10:45:55Z","publication":"bioRxiv","date_published":"2025-05-23T00:00:00Z","year":"2025","status":"public","OA_type":"green","publication_status":"submitted","month":"05","date_updated":"2025-12-30T10:54:12Z","day":"23","oa":1,"author":[{"full_name":"Cárdenas, Adrián","last_name":"Cárdenas","first_name":"Adrián"},{"last_name":"Çelik","full_name":"Çelik, Irem","first_name":"Irem"},{"first_name":"Alexandre","full_name":"Espinós, Alexandre","last_name":"Espinós"},{"first_name":"Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"full_name":"López-González, Lara","last_name":"López-González","first_name":"Lara"},{"first_name":"Lucia","full_name":"del-Valle-Anton, Lucia","last_name":"del-Valle-Anton"},{"first_name":"Virginia","full_name":"Fernández, Virginia","last_name":"Fernández"},{"first_name":"Salma","full_name":"Amin, Salma","last_name":"Amin"},{"first_name":"Enrico","full_name":"Negri, Enrico","last_name":"Negri"},{"first_name":"Eduardo Fernández","full_name":"Ortuño, Eduardo Fernández","last_name":"Ortuño"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Víctor","last_name":"Borrell","full_name":"Borrell, Víctor"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"article_processing_charge":"No","department":[{"_id":"SiHi"}],"citation":{"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>.","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>","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>","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>.","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.).","ieee":"A. Cárdenas <i>et al.</i>, “Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development,” <i>bioRxiv</i>. .","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>."},"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."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","OA_place":"repository","project":[{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}]},{"abstract":[{"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.","lang":"eng"}],"external_id":{"isi":["001163937900001"],"pmid":["38096816"]},"intvolume":"       112","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","ddc":["570"],"volume":112,"author":[{"orcid":"0000-0001-8457-2572","first_name":"Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T","last_name":"Cheung"},{"first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian"},{"full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","orcid":"0000-0002-3509-1948","first_name":"Peter"},{"last_name":"Krausgruber","full_name":"Krausgruber, Thomas","first_name":"Thomas"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher","first_name":"Carmen"},{"full_name":"Schrammel, Martin","id":"f13e7cae-e8bd-11ed-841a-96dedf69f46d","last_name":"Schrammel","first_name":"Martin"},{"full_name":"Özgen, Natalie Y","id":"e68ece33-f6e0-11ea-865d-ae1031dcc090","last_name":"Özgen","first_name":"Natalie Y"},{"first_name":"Alexis","last_name":"Ivec","id":"1d144691-e8be-11ed-9b33-bdd3077fad4c","full_name":"Ivec, Alexis"},{"last_name":"Bock","full_name":"Bock, Christoph","first_name":"Christoph"},{"orcid":"0000-0001-8761-9444","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"license":"https://creativecommons.org/licenses/by/4.0/","pmid":1,"oa":1,"article_processing_charge":"Yes (via OA deal)","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)"},"year":"2024","file":[{"date_updated":"2024-02-06T13:56:15Z","creator":"dernst","access_level":"open_access","file_size":5942467,"file_name":"2024_Neuron_Cheung.pdf","success":1,"content_type":"application/pdf","file_id":"14944","date_created":"2024-02-06T13:56:15Z","checksum":"32b3788f7085cf44a84108d8faaff3ce","relation":"main_file"}],"day":"17","status":"public","language":[{"iso":"eng"}],"has_accepted_license":"1","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. ","date_created":"2023-04-27T09:41:48Z","corr_author":"1","publication":"Neuron","doi":"10.1016/j.neuron.2023.11.009","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.","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.","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.","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>.","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>","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>.","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>"},"article_type":"original","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"}],"related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-pedigree-of-brain-cells/","relation":"press_release","description":"News on ISTA Website"}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"PreCl"}],"department":[{"_id":"SiHi"},{"_id":"RySh"}],"publication_identifier":{"issn":["0896-6273"]},"issue":"2","date_published":"2024-01-17T00:00:00Z","page":"230-246.e11","scopus_import":"1","date_updated":"2025-12-30T10:54:12Z","publication_status":"published","month":"01","publisher":"Elsevier","title":"Multipotent progenitors instruct ontogeny of the superior colliculus","oa_version":"Published Version","isi":1,"_id":"12875","type":"journal_article","file_date_updated":"2024-02-06T13:56:15Z"},{"article_number":"103157","oa":1,"pmid":1,"author":[{"orcid":"0000-0001-8457-2572","first_name":"Giselle T","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","last_name":"Cheung"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"article_processing_charge":"Yes","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["38935508"]},"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"}],"intvolume":"         5","volume":5,"APC_amount":"804 EUR","ddc":["570"],"quality_controlled":"1","OA_place":"publisher","has_accepted_license":"1","language":[{"iso":"eng"}],"doi":"10.1016/j.xpro.2024.103157","date_created":"2024-06-30T22:01:04Z","corr_author":"1","publication":"STAR Protocols","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).","file":[{"relation":"main_file","checksum":"d8a8cdba82a394e731aa699ace1ae433","success":1,"file_id":"18809","content_type":"application/pdf","date_created":"2025-01-09T12:12:40Z","file_name":"2024_STARProtoc_Cheung.pdf","file_size":5186071,"access_level":"open_access","creator":"dernst","date_updated":"2025-01-09T12:12:40Z"}],"year":"2024","status":"public","ec_funded":1,"OA_type":"gold","day":"20","publication_identifier":{"eissn":["2666-1667"]},"department":[{"_id":"SiHi"}],"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.","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.","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>.","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>","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>.","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>"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805"}],"article_type":"original","oa_version":"Published Version","title":"Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice","file_date_updated":"2025-01-09T12:12:40Z","type":"journal_article","_id":"17187","scopus_import":"1","issue":"3","date_published":"2024-09-20T00:00:00Z","publisher":"Elsevier","publication_status":"published","month":"09","date_updated":"2025-12-30T10:54:11Z"},{"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"related_material":{"link":[{"url":"https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/","description":"News on ISTA website","relation":"press_release"}]},"article_type":"original","project":[{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"T01031"}],"citation":{"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>","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>.","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>.","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>","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.","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.","short":"N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022)."},"publication_identifier":{"issn":["2375-2548"]},"department":[{"_id":"SiHi"}],"publisher":"American Association for the Advancement of Science","month":"11","publication_status":"published","date_updated":"2025-09-09T14:30:38Z","date_published":"2022-11-01T00:00:00Z","issue":"44","scopus_import":"1","file_date_updated":"2023-03-21T14:18:10Z","type":"journal_article","isi":1,"_id":"11336","oa_version":"Published Version","title":"Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression","volume":8,"ddc":["570"],"quality_controlled":"1","intvolume":"         8","external_id":{"pmid":["36322669"],"isi":["000918406800019"]},"abstract":[{"lang":"eng","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."}],"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)"},"article_processing_charge":"No","article_number":"abq1263","oa":1,"author":[{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","last_name":"Amberg","orcid":"0000-0002-3183-8207","first_name":"Nicole"},{"first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon"}],"pmid":1,"status":"public","day":"01","ec_funded":1,"file":[{"creator":"patrickd","date_updated":"2023-03-21T14:18:10Z","access_level":"open_access","file_size":2973998,"file_name":"sciadv.abq1263.pdf","content_type":"application/pdf","file_id":"12742","success":1,"date_created":"2023-03-21T14:18:10Z","checksum":"0117023e188542082ca6693cf39e7f03","relation":"main_file"}],"year":"2022","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.","corr_author":"1","publication":"Science Advances","date_created":"2022-04-26T15:04:50Z","has_accepted_license":"1","language":[{"iso":"eng"}]},{"oa":1,"article_number":"kvac009","author":[{"first_name":"Andi H","full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen"},{"last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","first_name":"Florian","orcid":"0000-0002-7462-0048"},{"orcid":"0000-0003-4844-6311","first_name":"Michael","full_name":"Riedl, Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","last_name":"Riedl"},{"first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher"},{"id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","full_name":"Heger, Anna-Magdalena","last_name":"Heger","first_name":"Anna-Magdalena"},{"last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne","first_name":"Susanne","orcid":"0000-0002-7903-3010"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","first_name":"Christoph M"},{"first_name":"Armel","full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas"},{"orcid":"0000-0003-2057-2754","first_name":"Björn","full_name":"Hof, Björn","id":"3A374330-F248-11E8-B48F-1D18A9856A87","last_name":"Hof"},{"last_name":"Tsai","full_name":"Tsai, Li Huei","first_name":"Li Huei"},{"full_name":"Rülicke, Thomas","last_name":"Rülicke","first_name":"Thomas"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"pmid":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)"},"article_processing_charge":"No","intvolume":"         1","external_id":{"pmid":["38596707"]},"abstract":[{"lang":"eng","text":"The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":1,"ddc":["570"],"quality_controlled":"1","has_accepted_license":"1","language":[{"iso":"eng"}],"doi":"10.1093/oons/kvac009","acknowledgement":"A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility.","corr_author":"1","publication":"Oxford Open Neuroscience","date_created":"2022-02-25T07:52:11Z","file":[{"file_size":4846551,"file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","date_updated":"2023-08-16T08:00:30Z","creator":"dernst","access_level":"open_access","relation":"main_file","date_created":"2023-08-16T08:00:30Z","file_id":"14061","content_type":"application/pdf","success":1,"checksum":"822e76e056c07099d1fb27d1ece5941b"}],"year":"2022","status":"public","day":"07","ec_funded":1,"publication_identifier":{"eissn":["2753-149X"]},"department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"citation":{"ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1). doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>","chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>. Oxford University Press, 2022. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>.","apa":"Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>","mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009, Oxford University Press, 2022, doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>.","short":"A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022).","ista":"Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009.","ieee":"A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1. Oxford University Press, 2022."},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"related_material":{"record":[{"relation":"dissertation_contains","id":"12726","status":"public"},{"id":"14530","relation":"dissertation_contains","status":"public"}]},"article_type":"original","project":[{"grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of radial neuronal migration"}],"oa_version":"Published Version","title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","type":"journal_article","file_date_updated":"2023-08-16T08:00:30Z","_id":"10791","issue":"1","date_published":"2022-07-07T00:00:00Z","publisher":"Oxford University Press","month":"07","date_updated":"2026-04-07T13:29:13Z","publication_status":"published"},{"publication":"Cell Reports","date_created":"2020-09-21T12:00:48Z","acknowledgement":"This work was supported by the program “Investissements d’avenir” ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under the European Union’s Horizon 2020 research and innovation programme grant agreement no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.” Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant, and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility, iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2 mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies. B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .","doi":"10.1016/j.celrep.2021.109208","language":[{"iso":"eng"}],"has_accepted_license":"1","ec_funded":1,"day":"08","status":"public","year":"2021","file":[{"file_size":8900385,"file_name":"2021_CellReports_Zhang.pdf","creator":"cziletti","date_updated":"2021-06-15T14:01:35Z","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"9554","success":1,"date_created":"2021-06-15T14:01:35Z","checksum":"7def3d42ebc8f5675efb6f38819e3e2e"}],"article_processing_charge":"No","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"pmid":1,"author":[{"last_name":"Zhang","full_name":"Zhang, Tingting","first_name":"Tingting"},{"full_name":"Liu, Tengyuan","last_name":"Liu","first_name":"Tengyuan"},{"first_name":"Natalia","last_name":"Mora","full_name":"Mora, Natalia"},{"first_name":"Justine","full_name":"Guegan, Justine","last_name":"Guegan"},{"full_name":"Bertrand, Mathilde","last_name":"Bertrand","first_name":"Mathilde"},{"first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","last_name":"Contreras"},{"first_name":"Andi H","full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen"},{"first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher"},{"first_name":"Marica","full_name":"Anderle, Marica","last_name":"Anderle"},{"last_name":"Danda","full_name":"Danda, Natasha","first_name":"Natasha"},{"first_name":"Luca","full_name":"Tiberi, Luca","last_name":"Tiberi"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"},{"first_name":"Bassem A.","last_name":"Hassan","full_name":"Hassan, Bassem A."}],"article_number":"109208","oa":1,"quality_controlled":"1","ddc":["570"],"volume":35,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","intvolume":"        35","abstract":[{"text":"Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated are unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, while intermediate levels of Notch activity generate inhibitory neurons, and daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors.","lang":"eng"}],"external_id":{"pmid":["34107249 "],"isi":["000659894300001"]},"_id":"8546","isi":1,"type":"journal_article","file_date_updated":"2021-06-15T14:01:35Z","title":"Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum","oa_version":"Published Version","month":"06","publication_status":"published","date_updated":"2026-04-02T11:52:30Z","publisher":"Elsevier","scopus_import":"1","issue":"10","date_published":"2021-06-08T00:00:00Z","department":[{"_id":"SiHi"}],"publication_identifier":{"eissn":[" 2211-1247"]},"project":[{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Molecular mechanisms of radial neuronal migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812"}],"article_type":"original","related_material":{"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.03.18.997205"}]},"citation":{"chicago":"Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand, Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” <i>Cell Reports</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">https://doi.org/10.1016/j.celrep.2021.109208</a>.","ama":"Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. <i>Cell Reports</i>. 2021;35(10). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">10.1016/j.celrep.2021.109208</a>","mla":"Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” <i>Cell Reports</i>, vol. 35, no. 10, 109208, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">10.1016/j.celrep.2021.109208</a>.","apa":"Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan, B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">https://doi.org/10.1016/j.celrep.2021.109208</a>","short":"T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen, C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell Reports 35 (2021).","ieee":"T. Zhang <i>et al.</i>, “Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum,” <i>Cell Reports</i>, vol. 35, no. 10. Elsevier, 2021.","ista":"Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. 35(10), 109208."}},{"issue":"12","date_published":"2021-06-22T00:00:00Z","scopus_import":"1","month":"06","publication_status":"published","date_updated":"2026-04-02T14:04:28Z","publisher":"Cell Press","title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis","oa_version":"Published Version","isi":1,"_id":"9603","file_date_updated":"2021-06-28T14:06:24Z","type":"journal_article","citation":{"ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. 2021;35(12). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>","chicago":"Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>. Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>.","mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>, vol. 35, no. 12, 109274, Cell Press, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>.","apa":"Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>","short":"X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen, T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo, T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).","ista":"Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274.","ieee":"X. Contreras <i>et al.</i>, “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” <i>Cell Reports</i>, vol. 35, no. 12. Cell Press, 2021."},"article_type":"original","project":[{"name":"Molecular mechanisms of radial neuronal migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/","relation":"press_release","description":"News on IST Homepage"}]},"department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"publication_identifier":{"eissn":["2211-1247"]},"year":"2021","file":[{"date_updated":"2021-06-28T14:06:24Z","creator":"asandaue","access_level":"open_access","file_size":7653149,"file_name":"2021_CellReports_Contreras.pdf","success":1,"file_id":"9613","content_type":"application/pdf","date_created":"2021-06-28T14:06:24Z","checksum":"d49520fdcbbb5c2f883bddb67cee5d77","relation":"main_file"}],"day":"22","ec_funded":1,"status":"public","language":[{"iso":"eng"}],"has_accepted_license":"1","acknowledgement":"We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 to S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H., 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.","publication":"Cell Reports","date_created":"2021-06-27T22:01:48Z","doi":"10.1016/j.celrep.2021.109274","external_id":{"isi":["000664463600016"],"pmid":["34161767"]},"intvolume":"        35","abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division."}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","quality_controlled":"1","ddc":["570"],"volume":35,"author":[{"full_name":"Contreras, Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","last_name":"Contreras","first_name":"Ximena"},{"last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","first_name":"Nicole","orcid":"0000-0002-3183-8207"},{"full_name":"Davaatseren, Amarbayasgalan","id":"70ADC922-B424-11E9-99E3-BA18E6697425","last_name":"Davaatseren","first_name":"Amarbayasgalan"},{"full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","first_name":"Andi H"},{"full_name":"Sonntag, Johanna","id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87","last_name":"Sonntag","first_name":"Johanna"},{"full_name":"Andersen, Lill","last_name":"Andersen","first_name":"Lill"},{"last_name":"Bernthaler","full_name":"Bernthaler, Tina","first_name":"Tina"},{"full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen"},{"first_name":"Anna-Magdalena","last_name":"Heger","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Randy L.","last_name":"Johnson","full_name":"Johnson, Randy L."},{"full_name":"Schwarz, Lindsay A.","last_name":"Schwarz","first_name":"Lindsay A."},{"full_name":"Luo, Liqun","last_name":"Luo","first_name":"Liqun"},{"full_name":"Rülicke, Thomas","last_name":"Rülicke","first_name":"Thomas"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon"}],"pmid":1,"oa":1,"article_number":"109274","article_processing_charge":"No","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"}},{"publisher":"Elsevier","publication_status":"published","date_updated":"2025-06-12T07:19:46Z","month":"09","issue":"6","date_published":"2020-09-23T00:00:00Z","page":"1160-1179.e9","scopus_import":"1","file_date_updated":"2020-12-02T09:26:46Z","type":"journal_article","isi":1,"_id":"8162","oa_version":"Published Version","title":"Cell-type specificity of genomic imprinting in cerebral cortex","related_material":{"link":[{"url":"https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/","relation":"press_release","description":"News on IST Website"}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"article_type":"original","project":[{"grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of radial neuronal migration"},{"name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"T01031"},{"grant_number":"M02416","_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"},{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002"},{"_id":"25D7962E-B435-11E9-9278-68D0E5697425","name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014"},{"call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444"},{"grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"citation":{"ama":"Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. 2020;107(6):1160-1179.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>","chicago":"Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>.","mla":"Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>.","apa":"Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher, C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>","short":"S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher, T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.","ista":"Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T, Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 107(6), 1160–1179.e9.","ieee":"S. Laukoter <i>et al.</i>, “Cell-type specificity of genomic imprinting in cerebral cortex,” <i>Neuron</i>, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020."},"publication_identifier":{"issn":["0896-6273"]},"department":[{"_id":"SiHi"}],"status":"public","day":"23","ec_funded":1,"year":"2020","file":[{"relation":"main_file","checksum":"7becdc16a6317304304631087ae7dd7f","date_created":"2020-12-02T09:26:46Z","file_id":"8828","success":1,"content_type":"application/pdf","file_name":"2020_Neuron_Laukoter.pdf","file_size":8911830,"access_level":"open_access","date_updated":"2020-12-02T09:26:46Z","creator":"dernst"}],"doi":"10.1016/j.neuron.2020.06.031","acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo for comments on earlier versions of the manuscript. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031). R.B. received support from the FWF Meitner-Programm (M 2416). This work was also supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement 618444 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","publication":"Neuron","date_created":"2020-07-23T16:03:12Z","corr_author":"1","has_accepted_license":"1","language":[{"iso":"eng"}],"volume":107,"quality_controlled":"1","ddc":["570"],"abstract":[{"lang":"eng","text":"In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity."}],"external_id":{"pmid":["32707083"],"isi":["000579698700006"]},"intvolume":"       107","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"article_processing_charge":"No","oa":1,"author":[{"last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne","first_name":"Susanne","orcid":"0000-0002-7903-3010"},{"first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Robert J","orcid":"0000-0002-8483-8753","last_name":"Beattie","full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-3183-8207","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","last_name":"Amberg"},{"first_name":"Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"first_name":"Thomas","full_name":"Penz, Thomas","last_name":"Penz"},{"orcid":"0000-0001-6091-3088","first_name":"Christoph","full_name":"Bock, Christoph","last_name":"Bock"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon"}],"pmid":1},{"article_processing_charge":"No","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)"},"pmid":1,"author":[{"full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","last_name":"Beattie","orcid":"0000-0002-8483-8753","first_name":"Robert J"},{"first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","last_name":"Amberg","orcid":"0000-0002-3183-8207","first_name":"Nicole"},{"first_name":"Giselle T","orcid":"0000-0001-8457-2572","last_name":"Cheung","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ximena","last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena"},{"first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H","last_name":"Hansen"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon"}],"article_number":"e61147","oa":1,"quality_controlled":"1","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Beginning from a limited pool of progenitors, the mammalian cerebral cortex forms highly organized functional neural circuits. However, the underlying cellular and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs) and eventual production of neurons and glia in the developing neuroepithelium remains unclear. Methods to trace NSC division patterns and map the lineage of clonally related cells have advanced dramatically. However, many contemporary lineage tracing techniques suffer from the lack of cellular resolution of progeny cell fate, which is essential for deciphering progenitor cell division patterns. Presented is a protocol using mosaic analysis with double markers (MADM) to perform in vivo clonal analysis. MADM concomitantly manipulates individual progenitor cells and visualizes precise division patterns and lineage progression at unprecedented single cell resolution. MADM-based interchromosomal recombination events during the G2-X phase of mitosis, together with temporally inducible CreERT2, provide exact information on the birth dates of clones and their division patterns. Thus, MADM lineage tracing provides unprecedented qualitative and quantitative optical readouts of the proliferation mode of stem cell progenitors at the single cell level. MADM also allows for examination of the mechanisms and functional requirements of candidate genes in NSC lineage progression. This method is unique in that comparative analysis of control and mutant subclones can be performed in the same tissue environment in vivo. Here, the protocol is described in detail, and experimental paradigms to employ MADM for clonal analysis and lineage tracing in the developing cerebral cortex are demonstrated. Importantly, this protocol can be adapted to perform MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver is present.","lang":"eng"}],"external_id":{"isi":["000546406600043"],"pmid":["32449730"]},"date_created":"2020-05-11T08:31:20Z","corr_author":"1","publication":"Journal of Visual Experiments","doi":"10.3791/61147","language":[{"iso":"eng"}],"has_accepted_license":"1","ec_funded":1,"day":"08","status":"public","file":[{"creator":"rbeattie","date_updated":"2020-07-14T12:48:03Z","access_level":"open_access","file_size":1352186,"file_name":"jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf","file_id":"7816","content_type":"application/pdf","date_created":"2020-05-11T08:28:38Z","checksum":"3154ea7f90b9fb45e084cd1c2770597d","relation":"main_file"}],"year":"2020","department":[{"_id":"SiHi"}],"publication_identifier":{"issn":["1940-087X"]},"project":[{"grant_number":"M02416","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"},{"call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425","name":"Role of Eed in neural stem cell lineage progression","grant_number":"T01031"},{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of radial neuronal migration"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"article_type":"original","related_material":{"record":[{"id":"7902","relation":"part_of_dissertation","status":"public"}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"citation":{"short":"R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen, S. Hippenmeyer, Journal of Visual Experiments (2020).","ista":"Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159), e61147.","ieee":"R. J. Beattie <i>et al.</i>, “Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM),” <i>Journal of Visual Experiments</i>, no. 159. MyJove Corporation, 2020.","chicago":"Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” <i>Journal of Visual Experiments</i>. MyJove Corporation, 2020. <a href=\"https://doi.org/10.3791/61147\">https://doi.org/10.3791/61147</a>.","ama":"Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). <i>Journal of Visual Experiments</i>. 2020;(159). doi:<a href=\"https://doi.org/10.3791/61147\">10.3791/61147</a>","apa":"Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen, A. H., &#38; Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). <i>Journal of Visual Experiments</i>. MyJove Corporation. <a href=\"https://doi.org/10.3791/61147\">https://doi.org/10.3791/61147</a>","mla":"Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” <i>Journal of Visual Experiments</i>, no. 159, e61147, MyJove Corporation, 2020, doi:<a href=\"https://doi.org/10.3791/61147\">10.3791/61147</a>."},"_id":"7815","isi":1,"type":"journal_article","file_date_updated":"2020-07-14T12:48:03Z","title":"Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM)","oa_version":"Published Version","month":"05","date_updated":"2026-07-07T22:30:55Z","publication_status":"published","publisher":"MyJove Corporation","scopus_import":"1","date_published":"2020-05-08T00:00:00Z","issue":"159"},{"publication_identifier":{"issn":["0021-8782"],"eissn":["1469-7580"]},"department":[{"_id":"SiHi"}],"citation":{"chicago":"Picco, Noemi, Simon Hippenmeyer, Julio Rodarte, Carmen Streicher, Zoltán Molnár, Philip K. Maini, and Thomas E. Woolley. “A Mathematical Insight into Cell Labelling Experiments for Clonal Analysis.” <i>Journal of Anatomy</i>. Wiley, 2019. <a href=\"https://doi.org/10.1111/joa.13001\">https://doi.org/10.1111/joa.13001</a>.","ama":"Picco N, Hippenmeyer S, Rodarte J, et al. A mathematical insight into cell labelling experiments for clonal analysis. <i>Journal of Anatomy</i>. 2019;235(3):686-696. doi:<a href=\"https://doi.org/10.1111/joa.13001\">10.1111/joa.13001</a>","mla":"Picco, Noemi, et al. “A Mathematical Insight into Cell Labelling Experiments for Clonal Analysis.” <i>Journal of Anatomy</i>, vol. 235, no. 3, Wiley, 2019, pp. 686–96, doi:<a href=\"https://doi.org/10.1111/joa.13001\">10.1111/joa.13001</a>.","apa":"Picco, N., Hippenmeyer, S., Rodarte, J., Streicher, C., Molnár, Z., Maini, P. K., &#38; Woolley, T. E. (2019). A mathematical insight into cell labelling experiments for clonal analysis. <i>Journal of Anatomy</i>. Wiley. <a href=\"https://doi.org/10.1111/joa.13001\">https://doi.org/10.1111/joa.13001</a>","short":"N. Picco, S. Hippenmeyer, J. Rodarte, C. Streicher, Z. Molnár, P.K. Maini, T.E. Woolley, Journal of Anatomy 235 (2019) 686–696.","ista":"Picco N, Hippenmeyer S, Rodarte J, Streicher C, Molnár Z, Maini PK, Woolley TE. 2019. A mathematical insight into cell labelling experiments for clonal analysis. Journal of Anatomy. 235(3), 686–696.","ieee":"N. Picco <i>et al.</i>, “A mathematical insight into cell labelling experiments for clonal analysis,” <i>Journal of Anatomy</i>, vol. 235, no. 3. Wiley, pp. 686–696, 2019."},"article_type":"original","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780"}],"oa_version":"Published Version","title":"A mathematical insight into cell labelling experiments for clonal analysis","type":"journal_article","file_date_updated":"2020-07-14T12:47:42Z","isi":1,"_id":"6844","date_published":"2019-09-01T00:00:00Z","page":"686-696","issue":"3","scopus_import":"1","publisher":"Wiley","date_updated":"2025-04-14T07:43:05Z","month":"09","publication_status":"published","oa":1,"author":[{"first_name":"Noemi","full_name":"Picco, Noemi","last_name":"Picco"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon"},{"last_name":"Rodarte","id":"3C70A038-F248-11E8-B48F-1D18A9856A87","full_name":"Rodarte, Julio","first_name":"Julio"},{"first_name":"Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"first_name":"Zoltán","full_name":"Molnár, Zoltán","last_name":"Molnár"},{"first_name":"Philip K.","last_name":"Maini","full_name":"Maini, Philip K."},{"first_name":"Thomas E.","last_name":"Woolley","full_name":"Woolley, Thomas E."}],"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"article_processing_charge":"No","abstract":[{"lang":"eng","text":"Studying the progression of the proliferative and differentiative patterns of neural stem cells at the individual cell level is crucial to the understanding of cortex development and how the disruption of such patterns can lead to malformations and neurodevelopmental diseases. However, our understanding of the precise lineage progression programme at single-cell resolution is still incomplete due to the technical variations in lineage- tracing approaches. One of the key challenges involves developing a robust theoretical framework in which we can integrate experimental observations and introduce correction factors to obtain a reliable and representative description of the temporal modulation of proliferation and differentiation. In order to obtain more conclusive insights, we carry out virtual clonal analysis using mathematical modelling and compare our results against experimental data. Using a dataset obtained with Mosaic Analysis with Double Markers, we illustrate how the theoretical description can be exploited to interpret and reconcile the disparity between virtual and experimental results."}],"external_id":{"isi":["000482426800017"]},"intvolume":"       235","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","volume":235,"quality_controlled":"1","ddc":["570"],"has_accepted_license":"1","language":[{"iso":"eng"}],"doi":"10.1111/joa.13001","date_created":"2019-09-02T11:57:28Z","publication":"Journal of Anatomy","year":"2019","file":[{"access_level":"open_access","date_updated":"2020-07-14T12:47:42Z","creator":"dernst","file_name":"2019_JournalAnatomy_Picco.pdf","file_size":1192994,"checksum":"160f960844b204057f20896e0e1f8ee7","file_id":"6845","content_type":"application/pdf","date_created":"2019-09-02T12:05:18Z","relation":"main_file"}],"status":"public","day":"01","ec_funded":1},{"_id":"7202","isi":1,"type":"journal_article","file_date_updated":"2020-07-14T12:47:53Z","title":"A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture","oa_version":"Published Version","date_updated":"2026-04-03T09:46:33Z","publication_status":"published","month":"11","publisher":"eLife Sciences Publications","scopus_import":"1","date_published":"2019-11-18T00:00:00Z","department":[{"_id":"SiHi"}],"publication_identifier":{"eissn":["2050-084X"]},"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"},{"name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","grant_number":"M02416"}],"article_type":"original","citation":{"short":"A. Llorca, G. Ciceri, R.J. Beattie, F.K. Wong, G. Diana, E. Serafeimidou-Pouliou, M. Fernández-Otero, C. Streicher, S.J. Arnold, M. Meyer, S. Hippenmeyer, M. Maravall, O. Marín, ELife 8 (2019).","ieee":"A. Llorca <i>et al.</i>, “A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","ista":"Llorca A, Ciceri G, Beattie RJ, Wong FK, Diana G, Serafeimidou-Pouliou E, Fernández-Otero M, Streicher C, Arnold SJ, Meyer M, Hippenmeyer S, Maravall M, Marín O. 2019. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. eLife. 8, e51381.","ama":"Llorca A, Ciceri G, Beattie RJ, et al. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.51381\">10.7554/eLife.51381</a>","chicago":"Llorca, Alfredo, Gabriele Ciceri, Robert J Beattie, Fong Kuan Wong, Giovanni Diana, Eleni Serafeimidou-Pouliou, Marian Fernández-Otero, et al. “A Stochastic Framework of Neurogenesis Underlies the Assembly of Neocortical Cytoarchitecture.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.51381\">https://doi.org/10.7554/eLife.51381</a>.","mla":"Llorca, Alfredo, et al. “A Stochastic Framework of Neurogenesis Underlies the Assembly of Neocortical Cytoarchitecture.” <i>ELife</i>, vol. 8, e51381, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.51381\">10.7554/eLife.51381</a>.","apa":"Llorca, A., Ciceri, G., Beattie, R. J., Wong, F. K., Diana, G., Serafeimidou-Pouliou, E., … Marín, O. (2019). A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.51381\">https://doi.org/10.7554/eLife.51381</a>"},"publication":"eLife","date_created":"2019-12-22T23:00:42Z","doi":"10.7554/eLife.51381","language":[{"iso":"eng"}],"has_accepted_license":"1","ec_funded":1,"day":"18","status":"public","year":"2019","file":[{"file_name":"2019_eLife_Llorca.pdf","file_size":2960543,"access_level":"open_access","date_updated":"2020-07-14T12:47:53Z","creator":"dernst","relation":"main_file","checksum":"b460ecc33e1a68265e7adea775021f3a","date_created":"2020-02-18T15:19:26Z","file_id":"7503","content_type":"application/pdf"}],"article_processing_charge":"No","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)"},"pmid":1,"author":[{"first_name":"Alfredo","last_name":"Llorca","full_name":"Llorca, Alfredo"},{"first_name":"Gabriele","last_name":"Ciceri","full_name":"Ciceri, Gabriele"},{"first_name":"Robert J","orcid":"0000-0002-8483-8753","last_name":"Beattie","full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Wong","full_name":"Wong, Fong Kuan","first_name":"Fong Kuan"},{"first_name":"Giovanni","full_name":"Diana, Giovanni","last_name":"Diana"},{"full_name":"Serafeimidou-Pouliou, Eleni","last_name":"Serafeimidou-Pouliou","first_name":"Eleni"},{"last_name":"Fernández-Otero","full_name":"Fernández-Otero, Marian","first_name":"Marian"},{"first_name":"Carmen","last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Arnold","full_name":"Arnold, Sebastian J.","first_name":"Sebastian J."},{"first_name":"Martin","full_name":"Meyer, Martin","last_name":"Meyer"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"},{"last_name":"Maravall","full_name":"Maravall, Miguel","first_name":"Miguel"},{"first_name":"Oscar","last_name":"Marín","full_name":"Marín, Oscar"}],"oa":1,"article_number":"e51381","quality_controlled":"1","ddc":["570"],"volume":8,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","external_id":{"isi":["000508156800001"],"pmid":["31736464"]},"abstract":[{"lang":"eng","text":"The cerebral cortex contains multiple areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modelling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas."}],"intvolume":"         8"},{"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"},{"call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex","grant_number":"M02416"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"The cerebral cortex contains multiple hierarchically organized areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have quantitatively investigated the neuronal output of individual progenitor cells in the ventricular zone of the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. We found that individual cortical progenitor cells show a high degree of stochasticity and generate pyramidal cell lineages that adopt a wide range of laminar configurations. Mathematical modelling these lineage data suggests that a small number of progenitor cell populations, each generating pyramidal cells following different stochastic developmental programs, suffice to generate the heterogenous complement of pyramidal cell lineages that collectively build the complex cytoarchitecture of the neocortex.","lang":"eng"}],"citation":{"ieee":"A. Llorca <i>et al.</i>, “Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture,” <i>bioRxiv</i>. .","ista":"Llorca A, Ciceri G, Beattie RJ, Wong FK, Diana G, Serafeimidou E, Fernández-Otero M, Streicher C, Arnold SJ, Meyer M, Hippenmeyer S, Maravall M, Marín O. Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture. bioRxiv, <a href=\"https://doi.org/10.1101/494088\">10.1101/494088</a>.","short":"A. Llorca, G. Ciceri, R.J. Beattie, F.K. Wong, G. Diana, E. Serafeimidou, M. Fernández-Otero, C. Streicher, S.J. Arnold, M. Meyer, S. Hippenmeyer, M. Maravall, O. Marín, BioRxiv (n.d.).","apa":"Llorca, A., Ciceri, G., Beattie, R. J., Wong, F. K., Diana, G., Serafeimidou, E., … Marín, O. (n.d.). Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/494088\">https://doi.org/10.1101/494088</a>","mla":"Llorca, Alfredo, et al. “Heterogeneous Progenitor Cell Behaviors Underlie the Assembly of Neocortical Cytoarchitecture.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/494088\">10.1101/494088</a>.","ama":"Llorca A, Ciceri G, Beattie RJ, et al. Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/494088\">10.1101/494088</a>","chicago":"Llorca, Alfredo, Gabriele Ciceri, Robert J Beattie, Fong K. Wong, Giovanni Diana, Eleni Serafeimidou, Marian Fernández-Otero, et al. “Heterogeneous Progenitor Cell Behaviors Underlie the Assembly of Neocortical Cytoarchitecture.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/494088\">https://doi.org/10.1101/494088</a>."},"article_processing_charge":"No","department":[{"_id":"SiHi"}],"oa":1,"author":[{"first_name":"Alfredo","last_name":"Llorca","full_name":"Llorca, Alfredo"},{"first_name":"Gabriele","full_name":"Ciceri, Gabriele","last_name":"Ciceri"},{"last_name":"Beattie","full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","orcid":"0000-0002-8483-8753"},{"first_name":"Fong K.","last_name":"Wong","full_name":"Wong, Fong K."},{"full_name":"Diana, Giovanni","last_name":"Diana","first_name":"Giovanni"},{"first_name":"Eleni","last_name":"Serafeimidou","full_name":"Serafeimidou, Eleni"},{"first_name":"Marian","full_name":"Fernández-Otero, Marian","last_name":"Fernández-Otero"},{"first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher"},{"last_name":"Arnold","full_name":"Arnold, Sebastian J.","first_name":"Sebastian J."},{"full_name":"Meyer, Martin","last_name":"Meyer","first_name":"Martin"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"},{"first_name":"Miguel","full_name":"Maravall, Miguel","last_name":"Maravall"},{"first_name":"Oscar","last_name":"Marín","full_name":"Marín, Oscar"}],"status":"public","ec_funded":1,"day":"13","month":"12","date_updated":"2026-07-06T12:52:50Z","publication_status":"submitted","year":"2018","date_published":"2018-12-13T00:00:00Z","type":"preprint","doi":"10.1101/494088","das_tickbox":"1","date_created":"2020-09-21T12:01:50Z","_id":"8547","publication":"bioRxiv","acknowledgement":"We thank I. Andrew and S.E. Bae for excellent technical assistance, F. Gage for plasmids, and K. Nave (Nex-Cre) for mouse colonies. We thank members of the Marín and Rico laboratories for stimulating discussions and ideas. Our research on this topic is supported by grants from the European Research Council (ERC-2017-AdG 787355 to O.M and ERC2016-CoG 725780 to S.H.) and Wellcome Trust (103714MA) to O.M. L.L. was the recipient of an EMBO long-term postdoctoral fellowship, R.B. received support from FWF Lise-Meitner program (M 2416) and F.K.W. was supported by an EMBO postdoctoral fellowship and is currently a Marie Skłodowska-Curie Fellow from the European Commission under the H2020 Programme.","main_file_link":[{"url":"https://doi.org/10.1101/494088","open_access":"1"}],"oa_version":"Preprint","title":"Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture","language":[{"iso":"eng"}]},{"author":[{"orcid":"0000-0002-8483-8753","first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","full_name":"Beattie, Robert J","last_name":"Beattie"},{"first_name":"Maria P","full_name":"Postiglione, Maria P","id":"2C67902A-F248-11E8-B48F-1D18A9856A87","last_name":"Postiglione"},{"last_name":"Burnett","full_name":"Burnett, Laura","id":"3B717F68-F248-11E8-B48F-1D18A9856A87","first_name":"Laura","orcid":"0000-0002-8937-410X"},{"full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter","orcid":"0000-0002-7903-3010","first_name":"Susanne"},{"first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher"},{"last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","orcid":"0000-0002-7462-0048"},{"full_name":"Xiao, Guanxi","last_name":"Xiao","first_name":"Guanxi"},{"full_name":"Klezovitch, Olga","last_name":"Klezovitch","first_name":"Olga"},{"full_name":"Vasioukhin, Valeri","last_name":"Vasioukhin","first_name":"Valeri"},{"last_name":"Ghashghaei","full_name":"Ghashghaei, Troy","first_name":"Troy"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"article_processing_charge":"No","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","intvolume":"        94","external_id":{"isi":["000400466700011"]},"abstract":[{"lang":"eng","text":"The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms."}],"quality_controlled":"1","volume":94,"language":[{"iso":"eng"}],"publication":"Neuron","corr_author":"1","date_created":"2018-12-11T11:49:20Z","doi":"10.1016/j.neuron.2017.04.012","year":"2017","publist_id":"6473","ec_funded":1,"day":"03","status":"public","department":[{"_id":"SiHi"},{"_id":"MaJö"}],"publication_identifier":{"issn":["0896-6273"]},"citation":{"short":"R.J. Beattie, M.P. Postiglione, L. Burnett, S. Laukoter, C. Streicher, F. Pauler, G. Xiao, O. Klezovitch, V. Vasioukhin, T. Ghashghaei, S. Hippenmeyer, Neuron 94 (2017) 517–533.e3.","ieee":"R. J. Beattie <i>et al.</i>, “Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells,” <i>Neuron</i>, vol. 94, no. 3. Cell Press, p. 517–533.e3, 2017.","ista":"Beattie RJ, Postiglione MP, Burnett L, Laukoter S, Streicher C, Pauler F, Xiao G, Klezovitch O, Vasioukhin V, Ghashghaei T, Hippenmeyer S. 2017. Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. Neuron. 94(3), 517–533.e3.","chicago":"Beattie, Robert J, Maria P Postiglione, Laura Burnett, Susanne Laukoter, Carmen Streicher, Florian Pauler, Guanxi Xiao, et al. “Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” <i>Neuron</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">https://doi.org/10.1016/j.neuron.2017.04.012</a>.","ama":"Beattie RJ, Postiglione MP, Burnett L, et al. Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. <i>Neuron</i>. 2017;94(3):517-533.e3. doi:<a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">10.1016/j.neuron.2017.04.012</a>","apa":"Beattie, R. J., Postiglione, M. P., Burnett, L., Laukoter, S., Streicher, C., Pauler, F., … Hippenmeyer, S. (2017). Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. <i>Neuron</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">https://doi.org/10.1016/j.neuron.2017.04.012</a>","mla":"Beattie, Robert J., et al. “Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” <i>Neuron</i>, vol. 94, no. 3, Cell Press, 2017, p. 517–533.e3, doi:<a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">10.1016/j.neuron.2017.04.012</a>."},"project":[{"name":"Molecular Mechanisms of Cerebral Cortex Development","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618444"},{"grant_number":"RGP0053/2014","name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","_id":"25D7962E-B435-11E9-9278-68D0E5697425"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"title":"Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells","oa_version":"None","_id":"944","isi":1,"type":"journal_article","scopus_import":"1","date_published":"2017-05-03T00:00:00Z","page":"517 - 533.e3","issue":"3","date_updated":"2026-04-16T09:57:27Z","month":"05","publication_status":"published","publisher":"Cell Press"},{"publist_id":"5621","year":"2015","status":"public","day":"02","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560602/"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2015.07.011","acknowledgement":"Research in the G.F. laboratory is supported by NIH (NS 081297, MH095147, and P01NS074972) and the Simons Foundation. Research in the S.H. laboratory is supported by the European Union (FP7-CIG618444). C.M. is supported by EMBO ALTF (1295-2012). X.H.J. is supported by EMBO (ALTF 303-2010) and HFSP (LT000078/2011-L).\r\n\r\n","publication":"Neuron","date_created":"2018-12-11T11:52:40Z","intvolume":"        87","external_id":{"pmid":["26299473"],"isi":["000361146300009"]},"abstract":[{"lang":"eng","text":"The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute."}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","volume":87,"quality_controlled":"1","oa":1,"author":[{"last_name":"Mayer","full_name":"Mayer, Christian","first_name":"Christian"},{"first_name":"Xavier","last_name":"Jaglin","full_name":"Jaglin, Xavier"},{"full_name":"Cobbs, Lucy","last_name":"Cobbs","first_name":"Lucy"},{"last_name":"Bandler","full_name":"Bandler, Rachel","first_name":"Rachel"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher","first_name":"Carmen"},{"first_name":"Constance","full_name":"Cepko, Constance","last_name":"Cepko"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Fishell, Gord","last_name":"Fishell","first_name":"Gord"}],"pmid":1,"article_processing_charge":"No","page":"989 - 998","issue":"5","date_published":"2015-09-02T00:00:00Z","scopus_import":"1","publisher":"Elsevier","publication_status":"published","date_updated":"2025-09-23T08:16:35Z","month":"09","oa_version":"Submitted Version","title":"Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries","type":"journal_article","isi":1,"_id":"1550","citation":{"chicago":"Mayer, Christian, Xavier Jaglin, Lucy Cobbs, Rachel Bandler, Carmen Streicher, Constance Cepko, Simon Hippenmeyer, and Gord Fishell. “Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional Areas and Structural Boundaries.” <i>Neuron</i>. Elsevier, 2015. <a href=\"https://doi.org/10.1016/j.neuron.2015.07.011\">https://doi.org/10.1016/j.neuron.2015.07.011</a>.","ama":"Mayer C, Jaglin X, Cobbs L, et al. Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries. <i>Neuron</i>. 2015;87(5):989-998. doi:<a href=\"https://doi.org/10.1016/j.neuron.2015.07.011\">10.1016/j.neuron.2015.07.011</a>","mla":"Mayer, Christian, et al. “Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional Areas and Structural Boundaries.” <i>Neuron</i>, vol. 87, no. 5, Elsevier, 2015, pp. 989–98, doi:<a href=\"https://doi.org/10.1016/j.neuron.2015.07.011\">10.1016/j.neuron.2015.07.011</a>.","apa":"Mayer, C., Jaglin, X., Cobbs, L., Bandler, R., Streicher, C., Cepko, C., … Fishell, G. (2015). Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2015.07.011\">https://doi.org/10.1016/j.neuron.2015.07.011</a>","short":"C. Mayer, X. Jaglin, L. Cobbs, R. Bandler, C. Streicher, C. Cepko, S. Hippenmeyer, G. Fishell, Neuron 87 (2015) 989–998.","ista":"Mayer C, Jaglin X, Cobbs L, Bandler R, Streicher C, Cepko C, Hippenmeyer S, Fishell G. 2015. Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries. Neuron. 87(5), 989–998.","ieee":"C. Mayer <i>et al.</i>, “Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries,” <i>Neuron</i>, vol. 87, no. 5. Elsevier, pp. 989–998, 2015."},"department":[{"_id":"SiHi"}]},{"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","external_id":{"isi":["000344522000011"]},"intvolume":"       159","abstract":[{"lang":"eng","text":"Radial glial progenitors (RGPs) are responsible for producing nearly all neocortical neurons. To gain insight into the patterns of RGP division and neuron production, we quantitatively analyzed excitatory neuron genesis in the mouse neocortex using Mosaic Analysis with Double Markers, which provides single-cell resolution of progenitor division patterns and potential in vivo. We found that RGPs progress through a coherent program in which their proliferative potential diminishes in a predictable manner. Upon entry into the neurogenic phase, individual RGPs produce ∼8–9 neurons distributed in both deep and superficial layers, indicating a unitary output in neuronal production. Removal of OTX1, a transcription factor transiently expressed in RGPs, results in both deep- and superficial-layer neuron loss and a reduction in neuronal unit size. Moreover, ∼1/6 of neurogenic RGPs proceed to produce glia. These results suggest that progenitor behavior and histogenesis in the mammalian neocortex conform to a remarkably orderly and deterministic program."}],"ddc":["570"],"quality_controlled":"1","volume":159,"author":[{"full_name":"Gao, Peng","last_name":"Gao","first_name":"Peng"},{"first_name":"Maria P","id":"2C67902A-F248-11E8-B48F-1D18A9856A87","full_name":"Postiglione, Maria P","last_name":"Postiglione"},{"first_name":"Teresa","full_name":"Krieger, Teresa","last_name":"Krieger"},{"full_name":"Hernandez, Luisirene","last_name":"Hernandez","first_name":"Luisirene"},{"last_name":"Wang","full_name":"Wang, Chao","first_name":"Chao"},{"last_name":"Han","full_name":"Han, Zhi","first_name":"Zhi"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher","first_name":"Carmen"},{"full_name":"Papusheva, Ekaterina","id":"41DB591E-F248-11E8-B48F-1D18A9856A87","last_name":"Papusheva","first_name":"Ekaterina"},{"last_name":"Insolera","full_name":"Insolera, Ryan","first_name":"Ryan"},{"first_name":"Kritika","full_name":"Chugh, Kritika","last_name":"Chugh"},{"first_name":"Oren","full_name":"Kodish, Oren","last_name":"Kodish"},{"last_name":"Huang","full_name":"Huang, Kun","first_name":"Kun"},{"last_name":"Simons","full_name":"Simons, Benjamin","first_name":"Benjamin"},{"first_name":"Liqun","full_name":"Luo, Liqun","last_name":"Luo"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061"},{"full_name":"Shi, Song","last_name":"Shi","first_name":"Song"}],"oa":1,"article_processing_charge":"No","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)"},"year":"2014","file":[{"relation":"main_file","date_created":"2018-12-12T10:08:47Z","content_type":"application/pdf","file_id":"4709","checksum":"6c5de8329bb2ffa71cba9fda750f14ce","file_size":4435787,"file_name":"IST-2016-423-v1+1_1-s2.0-S0092867414013154-main.pdf","date_updated":"2020-07-14T12:45:25Z","creator":"system","access_level":"open_access"}],"publist_id":"5050","ec_funded":1,"day":"06","status":"public","language":[{"iso":"eng"}],"has_accepted_license":"1","corr_author":"1","publication":"Cell","date_created":"2018-12-11T11:55:16Z","doi":"10.1016/j.cell.2014.10.027","citation":{"apa":"Gao, P., Postiglione, M. P., Krieger, T., Hernandez, L., Wang, C., Han, Z., … Shi, S. (2014). Deterministic progenitor behavior and unitary production of neurons in the neocortex. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2014.10.027\">https://doi.org/10.1016/j.cell.2014.10.027</a>","mla":"Gao, Peng, et al. “Deterministic Progenitor Behavior and Unitary Production of Neurons in the Neocortex.” <i>Cell</i>, vol. 159, no. 4, Cell Press, 2014, pp. 775–88, doi:<a href=\"https://doi.org/10.1016/j.cell.2014.10.027\">10.1016/j.cell.2014.10.027</a>.","ama":"Gao P, Postiglione MP, Krieger T, et al. Deterministic progenitor behavior and unitary production of neurons in the neocortex. <i>Cell</i>. 2014;159(4):775-788. doi:<a href=\"https://doi.org/10.1016/j.cell.2014.10.027\">10.1016/j.cell.2014.10.027</a>","chicago":"Gao, Peng, Maria P Postiglione, Teresa Krieger, Luisirene Hernandez, Chao Wang, Zhi Han, Carmen Streicher, et al. “Deterministic Progenitor Behavior and Unitary Production of Neurons in the Neocortex.” <i>Cell</i>. Cell Press, 2014. <a href=\"https://doi.org/10.1016/j.cell.2014.10.027\">https://doi.org/10.1016/j.cell.2014.10.027</a>.","ista":"Gao P, Postiglione MP, Krieger T, Hernandez L, Wang C, Han Z, Streicher C, Papusheva E, Insolera R, Chugh K, Kodish O, Huang K, Simons B, Luo L, Hippenmeyer S, Shi S. 2014. Deterministic progenitor behavior and unitary production of neurons in the neocortex. Cell. 159(4), 775–788.","ieee":"P. Gao <i>et al.</i>, “Deterministic progenitor behavior and unitary production of neurons in the neocortex,” <i>Cell</i>, vol. 159, no. 4. Cell Press, pp. 775–788, 2014.","short":"P. Gao, M.P. Postiglione, T. Krieger, L. Hernandez, C. Wang, Z. Han, C. Streicher, E. Papusheva, R. Insolera, K. Chugh, O. Kodish, K. Huang, B. Simons, L. Luo, S. Hippenmeyer, S. Shi, Cell 159 (2014) 775–788."},"project":[{"name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444"},{"grant_number":"RGP0053/2014","name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","_id":"25D7962E-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"SiHi"},{"_id":"Bio"}],"scopus_import":"1","pubrep_id":"423","page":"775 - 788","issue":"4","date_published":"2014-11-06T00:00:00Z","month":"11","date_updated":"2025-09-29T11:57:49Z","publication_status":"published","publisher":"Cell Press","title":"Deterministic progenitor behavior and unitary production of neurons in the neocortex","oa_version":"Published Version","_id":"2022","isi":1,"type":"journal_article","file_date_updated":"2020-07-14T12:45:25Z"}]