[{"status":"public","OA_place":"repository","citation":{"ista":"Jiang Y, Ahn R, Huang A, Gonzalez PP, Kim J, Zhang G, Liu Z, He Z, Dudley L, Patel KS, Dzhivhuho GA, Crowl S, Przanowski P, Camacho LQ, Hao S, Zeng J, Hippenmeyer S, Fallahi-Sichani M, Janes KA, Naegle KM, Hammarskjold M-L, Goldman SA, Kornblum HI, Yao M, White F, Zong H. 2026. Critical role of cell competition in gliomagenesis. bioRxiv, <a href=\"https://doi.org/10.64898/2026.01.15.699808\">10.64898/2026.01.15.699808</a>.","ieee":"Y. Jiang <i>et al.</i>, “Critical role of cell competition in gliomagenesis,” <i>bioRxiv</i>. 2026.","short":"Y. Jiang, R. Ahn, A. Huang, P.P. Gonzalez, J. Kim, G. Zhang, Z. Liu, Z. He, L. Dudley, K.S. Patel, G.A. Dzhivhuho, S. Crowl, P. Przanowski, L.Q. Camacho, S. Hao, J. Zeng, S. Hippenmeyer, M. Fallahi-Sichani, K.A. Janes, K.M. Naegle, M.-L. Hammarskjold, S.A. Goldman, H.I. Kornblum, M. Yao, F. White, H. Zong, BioRxiv (2026).","mla":"Jiang, Ying, et al. “Critical Role of Cell Competition in Gliomagenesis.” <i>BioRxiv</i>, 2026, doi:<a href=\"https://doi.org/10.64898/2026.01.15.699808\">10.64898/2026.01.15.699808</a>.","ama":"Jiang Y, Ahn R, Huang A, et al. Critical role of cell competition in gliomagenesis. <i>bioRxiv</i>. 2026. doi:<a href=\"https://doi.org/10.64898/2026.01.15.699808\">10.64898/2026.01.15.699808</a>","apa":"Jiang, Y., Ahn, R., Huang, A., Gonzalez, P. P., Kim, J., Zhang, G., … Zong, H. (2026). Critical role of cell competition in gliomagenesis. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.01.15.699808\">https://doi.org/10.64898/2026.01.15.699808</a>","chicago":"Jiang, Ying, Ryuhjin Ahn, Arthur Huang, Phillippe P. Gonzalez, Jungeun Kim, Guoxin Zhang, Zihao Liu, et al. “Critical Role of Cell Competition in Gliomagenesis.” <i>BioRxiv</i>, 2026. <a href=\"https://doi.org/10.64898/2026.01.15.699808\">https://doi.org/10.64898/2026.01.15.699808</a>."},"ddc":["570"],"day":"16","_id":"21212","type":"preprint","article_processing_charge":"No","oa_version":"Preprint","acknowledgement":"We thank Dr. Wenjie Liu for providing critical feedback on the manuscript. We also thank Dr.\r\nPat Pramoonjago at the Biorepository and Tissue Research Facility, and Hope Davis at the\r\nvivarium for their assistance on the project. These Core Facilities are supported by UVA Cancer\r\nCenter grant #P30-CA044579. We are grateful to Dr. Jonathan A. Epstein for providing the\r\nNf1GRD/+ mouse strain (https://pubmed.ncbi.nlm.nih.gov/26460546/). This work was partly\r\nsupported by the National Institute of Neurological Diseases and Stroke R21 NS125479-01A1\r\n(H.Z.), American Cancer Society Institutional Research Grant to the University of Virginia\r\n(Y.J.), the National Natural Science Foundation of China #82072787 (M.Y.), the National\r\nCancer Institute U54 CA238114 (F.W.), U01 CA284193 (K.M.N.), and U54 CA274499 (K.A.J.,\r\nM.F-S.), the National institute of General Medical Sciences R35 GM133404 (M.F-S.), the Dr.\r\nMiriam and Sheldon G. Adelson Medical Research Foundation (H.I.K., S.A.G.), the National\r\nCenter for Advancing Translational Sciences KL2TR001882 (K.S.P.), Tower Cancer Career Development Grant (K.S.P.), McKnight Neurobiology of Brain Disorders Grant (K.S.P.). The\r\ncontent is solely the responsibility of the authors and does not necessarily represent the official\r\nviews of the National Institutes of Health. Illustrations in this manuscript were created with\r\nBioRender (BioRender.com).","department":[{"_id":"SiHi"}],"date_updated":"2026-02-16T10:12:42Z","main_file_link":[{"url":"https://doi.org/10.64898/2026.01.15.699808","open_access":"1"}],"abstract":[{"lang":"eng","text":"Malignant glioma is incurable. Using a mouse genetic mosaic system to generate sporadic Trp53,Nf1-null OPCs, we previously identified oligodendrocyte precursor cell (OPC) as a cell-of-origin of glioma. Here, we report that pre-malignant Trp53,Nf1-null OPCs outcompete wildtype counterparts during their expansion. Blocking competition by mutating/strengthening wildtype OPCs impeded both pre-malignant progression and malignant expansion of glioma.\r\n\r\n“In-tissue” phosphoproteomic profiling revealed an enrichment of phosphopeptides related to RNA splicing and protein translation at the peak of cell competition, suggesting that competitiveness may stem from unique protein species. Among candidates was mTORC1, whose pharmacological inhibition or genetic disruption resulted in a loss of competitiveness in our mouse model. Finally, analysis of patient biopsies and interrogating the role of individual gliomagenic mutations in OPC competition supported its relevance in human gliomas. Together, these findings identified the driving role of competitive interactions among OPCs in gliomagenesis, and suggest unconventional therapeutic strategies to target this process."}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","month":"01","date_created":"2026-02-10T12:55:55Z","author":[{"full_name":"Jiang, Ying","last_name":"Jiang","first_name":"Ying"},{"full_name":"Ahn, Ryuhjin","last_name":"Ahn","first_name":"Ryuhjin"},{"full_name":"Huang, Arthur","last_name":"Huang","first_name":"Arthur"},{"first_name":"Phillippe P.","last_name":"Gonzalez","full_name":"Gonzalez, Phillippe P."},{"full_name":"Kim, Jungeun","first_name":"Jungeun","last_name":"Kim"},{"first_name":"Guoxin","last_name":"Zhang","full_name":"Zhang, Guoxin"},{"full_name":"Liu, Zihao","last_name":"Liu","first_name":"Zihao"},{"first_name":"Zhenqiang","last_name":"He","full_name":"He, Zhenqiang"},{"full_name":"Dudley, Lindsey","first_name":"Lindsey","last_name":"Dudley"},{"full_name":"Patel, Kunal S.","first_name":"Kunal S.","last_name":"Patel"},{"full_name":"Dzhivhuho, Godfrey A.","last_name":"Dzhivhuho","first_name":"Godfrey A."},{"full_name":"Crowl, Sam","first_name":"Sam","last_name":"Crowl"},{"full_name":"Przanowski, Piotr","first_name":"Piotr","last_name":"Przanowski"},{"last_name":"Camacho","first_name":"Luisa Quesada","full_name":"Camacho, Luisa Quesada"},{"first_name":"Sijie","last_name":"Hao","full_name":"Hao, Sijie"},{"full_name":"Zeng, Jianhao","first_name":"Jianhao","last_name":"Zeng"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061"},{"full_name":"Fallahi-Sichani, Mohammad","last_name":"Fallahi-Sichani","first_name":"Mohammad"},{"full_name":"Janes, Kevin A.","first_name":"Kevin A.","last_name":"Janes"},{"full_name":"Naegle, Kristen M.","first_name":"Kristen M.","last_name":"Naegle"},{"full_name":"Hammarskjold, Marie-Louise","first_name":"Marie-Louise","last_name":"Hammarskjold"},{"first_name":"Steven A.","last_name":"Goldman","full_name":"Goldman, Steven A."},{"last_name":"Kornblum","first_name":"Harley I.","full_name":"Kornblum, Harley I."},{"first_name":"Maojin","last_name":"Yao","full_name":"Yao, Maojin"},{"full_name":"White, Forest","first_name":"Forest","last_name":"White"},{"first_name":"Hui","last_name":"Zong","full_name":"Zong, Hui"}],"title":"Critical role of cell competition in gliomagenesis","OA_type":"green","date_published":"2026-01-16T00:00:00Z","doi":"10.64898/2026.01.15.699808","has_accepted_license":"1","year":"2026","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"publication_status":"published","language":[{"iso":"eng"}],"publication":"bioRxiv","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"}},{"citation":{"apa":"Polat Haas, F., Villalba Requena, A., Rusina, P., Gopalan, A., Fritz, H., Akhmetkaliyev, A., … Keller Valsecchi, C. I. (n.d.). The splicing paralogues SNRPB and SNRPN control differential metabolic states. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.02.11.705284\">https://doi.org/10.64898/2026.02.11.705284</a>","ama":"Polat Haas F, Villalba Requena A, Rusina P, et al. The splicing paralogues SNRPB and SNRPN control differential metabolic states. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.64898/2026.02.11.705284\">10.64898/2026.02.11.705284</a>","chicago":"Polat Haas, Feyza, Ana Villalba Requena, Polina Rusina, Anusha Gopalan, Hector Fritz, Azamat Akhmetkaliyev, Frank Ruehle, et al. “The Splicing Paralogues SNRPB and SNRPN Control Differential Metabolic States.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.64898/2026.02.11.705284\">https://doi.org/10.64898/2026.02.11.705284</a>.","ista":"Polat Haas F, Villalba Requena A, Rusina P, Gopalan A, Fritz H, Akhmetkaliyev A, Ruehle F, Einsiedel A, Szczepinska A, Kielisch F, Chen J-X, Nguyen S, Schmidlin T, Hippenmeyer S, Bailicata MF, Keller Valsecchi CI. The splicing paralogues SNRPB and SNRPN control differential metabolic states. bioRxiv, <a href=\"https://doi.org/10.64898/2026.02.11.705284\">10.64898/2026.02.11.705284</a>.","ieee":"F. Polat Haas <i>et al.</i>, “The splicing paralogues SNRPB and SNRPN control differential metabolic states.,” <i>bioRxiv</i>. .","short":"F. Polat Haas, A. Villalba Requena, P. Rusina, A. Gopalan, H. Fritz, A. Akhmetkaliyev, F. Ruehle, A. Einsiedel, A. Szczepinska, F. Kielisch, J.-X. Chen, S. Nguyen, T. Schmidlin, S. Hippenmeyer, M.F. Bailicata, C.I. Keller Valsecchi, BioRxiv (n.d.).","mla":"Polat Haas, Feyza, et al. “The Splicing Paralogues SNRPB and SNRPN Control Differential Metabolic States.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.64898/2026.02.11.705284\">10.64898/2026.02.11.705284</a>."},"OA_place":"repository","status":"public","acknowledgement":"We thank Oliver Mühlemann and Alex Hofer (University of Bern) for sharing SMG inhibitors\r\nand for their expertise in nonsense-mediated mRNA decay and Maria Hondele for critical\r\nreading of the manuscript draft. We also thank the IMB Genomics Core Facility for assistance\r\nwith library preparation and sequencing, Martin Möckel and the IMB Protein Production Core\r\nFacility for providing enzymes used in this work, Marton Gelleri together with the IMB\r\nMicroscopy Core Facility for support with microscopy and FRAP experiments, Jasmin Cartano\r\nfor proteomics sample processing and the IMB Flow Cytometry Core Facility for support. In\r\naddition, we thank the Imaging Core Facility (IMCF) and the FACS Core Facility at the\r\nBiozentrum, University of Basel, for technical assistance. CIKV acknowledges funding by the\r\nDeutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Individual Grant\r\nProject no. 513744403, Scientific Network Grant Project no. 531902894, GRK2526 “Genevo”\r\n- Project no. 407023052”, GRK2859 (“4R”) - Project no. 491145305, Forschungsinitiative\r\nRheinland-Pfalz (ReALity), the EMBO Young Investigator Program (5795), institutional\r\nfunding from the Institute of Molecular Biology and funds from the Kanton Basel-Stadt and\r\nBasel-Land provided to the Biozentrum of the University Basel. J.H.G.F.G. was part of the\r\n‘Science of Healthy Ageing Research Programme’ (SHARP) initiative funded by RhinelandPalatinate’s Ministry of Science, Education and Culture. PR is funded by the Biozentrum PhD\r\nFellowships Program. MFB received financial support from the intramural High Potentials\r\nGrant program of the University Medical Center Mainz, Forschungsinitiative Rheinland-Pfalz\r\n(ReALity) and Stiftungen zugunsten der Medizinischen Fakultät der LMU Klinikum (26069).\r\nInstruments in the IMB core facilities were supported by funds from the DFG: Laser Scanning\r\nConfocal (Leica Stellaris 8 Falcon, funded by the DFG - Project #497669232), Orbitrap Astral system (funded by the DFG - Project #524805621) and BD LSRFortessa SOPR is funded by\r\nthe DFG - Project #210253511.\r\n","department":[{"_id":"SiHi"}],"oa_version":"Preprint","article_processing_charge":"No","type":"preprint","_id":"21290","day":"11","author":[{"first_name":"Feyza","last_name":"Polat Haas","full_name":"Polat Haas, Feyza"},{"orcid":"0000-0002-5615-5277","last_name":"Villalba Requena","first_name":"Ana","full_name":"Villalba Requena, Ana","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247"},{"last_name":"Rusina","first_name":"Polina","full_name":"Rusina, Polina"},{"full_name":"Gopalan, Anusha","first_name":"Anusha","last_name":"Gopalan"},{"full_name":"Fritz, Hector","first_name":"Hector","last_name":"Fritz"},{"last_name":"Akhmetkaliyev","first_name":"Azamat","full_name":"Akhmetkaliyev, Azamat"},{"last_name":"Ruehle","first_name":"Frank","full_name":"Ruehle, Frank"},{"first_name":"Anna","last_name":"Einsiedel","full_name":"Einsiedel, Anna"},{"full_name":"Szczepinska, Anna","last_name":"Szczepinska","first_name":"Anna"},{"full_name":"Kielisch, Fridolin","first_name":"Fridolin","last_name":"Kielisch"},{"first_name":"Jia-Xuan","last_name":"Chen","full_name":"Chen, Jia-Xuan"},{"last_name":"Nguyen","first_name":"Susanne","full_name":"Nguyen, Susanne"},{"first_name":"Thierry","last_name":"Schmidlin","full_name":"Schmidlin, Thierry"},{"orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"},{"last_name":"Bailicata","first_name":"M. Felicia","full_name":"Bailicata, M. Felicia"},{"first_name":"Claudia Isabelle","last_name":"Keller Valsecchi","full_name":"Keller Valsecchi, Claudia Isabelle"}],"title":"The splicing paralogues SNRPB and SNRPN control differential metabolic states.","date_created":"2026-02-17T11:35:59Z","month":"02","abstract":[{"text":"Gene duplication underlies evolutionary innovation, yet many paralogues remain highly similar, raising questions about their functional divergence and physiological relevance. The spliceosomal Sm core protein SNRPB and its mammalian-specific paralogue SNRPN share over 90% sequence identity, but their distinct expression patterns - SNRPB being ubiquitous and SNRPN confined to the brain - suggest specialized functions. Why mammals have two different spliceosomes has remained obscure. Here, we generated isogenic human cell lines expressing ectopically either SNRPB or SNRPN exclusively and found that SNRPN stabilizes transcripts involved in energy metabolism and mitochondrial function, leading to increased mitochondrial abundance and oxygen consumption. Despite similar spliceosomal interactomes, SNRPN more strongly associates with the PRMT5 methylosome complex and exhibits dynamic arginine methylation in its C-terminal region that is sensitive to translation inhibition and amino acid availability. The SNRPN-dependent transcriptome responds to translation inhibition by stabilizing long, intron-rich genes involved in amino acid and energy metabolism. Our findings reveal a nutrient-sensitive, methylation-dependent mechanism that differentiates the two paralogues. This suggests that SNRPN functions as a metabolic-specialized spliceosomal subunit thereby providing tissue-specific adaptation of RNA processing in mammals.","lang":"eng"}],"main_file_link":[{"url":"https://doi.org/10.64898/2026.02.11.705284","open_access":"1"}],"date_updated":"2026-02-23T11:03:33Z","publication":"bioRxiv","language":[{"iso":"eng"}],"oa":1,"publication_status":"submitted","year":"2026","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.64898/2026.02.11.705284","date_published":"2026-02-11T00:00:00Z","OA_type":"green"},{"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. ","type":"preprint","OA_place":"repository","status":"public","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"year":"2026","oa":1,"doi":"10.64898/2026.02.12.705305","has_accepted_license":"1","month":"02","department":[{"_id":"SiHi"},{"_id":"LoSw"}],"_id":"21291","oa_version":"Preprint","article_processing_charge":"No","day":"16","ddc":["570"],"citation":{"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>.","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>","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>","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.).","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>.","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>."},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"publication":"bioRxiv","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"submitted","corr_author":"1","OA_type":"green","date_published":"2026-02-16T00:00:00Z","date_created":"2026-02-17T11:36:20Z","title":"Lineage origin of spinal cord cell type diversity","author":[{"first_name":"Sophie A","last_name":"Gobeil","full_name":"Gobeil, Sophie A","id":"2f3e9efb-eb24-11ec-86b2-88efb11d59fa"},{"first_name":"Francisco","last_name":"Da Silveira Neto","id":"8cfb7412-10a7-11f1-add1-82b44e6418f2","full_name":"Da Silveira Neto, Francisco"},{"first_name":"Giulia","last_name":"Silvestrelli","id":"12632ae8-799e-11ef-94a2-e5a3b5ef49e9","full_name":"Silvestrelli, Giulia"},{"last_name":"Smits","first_name":"Matthijs Geert","id":"7a231d52-e216-11ee-a0bb-8acd55f8f1f0","full_name":"Smits, Matthijs Geert"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher","first_name":"Carmen"},{"orcid":"0000-0001-8457-2572","last_name":"Cheung","first_name":"Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061"},{"last_name":"Sweeney","first_name":"Lora Beatrice Jaeger","orcid":"0000-0001-9242-5601","full_name":"Sweeney, Lora Beatrice Jaeger","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425"}],"project":[{"name":"Development and Evolution of Tetrapod Motor Circuits","grant_number":"101041551","_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae"},{"_id":"8da85f50-16d5-11f0-9cad-eab8b0ff6c9e","grant_number":"F7814","name":"Stem Cell Modulation in Neural Development and Regeneration/ P14-Swim-to-limb transition: cell type to connection diversity"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"}],"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"}],"date_updated":"2026-04-14T08:16:55Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.64898/2026.02.12.705305"}]},{"volume":99,"OA_place":"publisher","status":"public","publication_identifier":{"issn":["0959-437X"],"eissn":["1879-0380"]},"acknowledgement":"We wish to thank all members of the Hippenmeyer laboratory at ISTA for exciting discussions on the subject of this review. We apologize to colleagues whose work we could not cite and/or discuss in the frame of the available space. Work in the Hippenmeyer laboratory on the discussed topic is supported by ISTA institutional funds, an EMBO LTF (ALTF 994–2023) to F.P., FWF SFB F78 (10.55776/F78) to S.H., and FWF Cluster of Excellence COE16 (10.55776/COE16) to S.H.","type":"journal_article","license":"https://creativecommons.org/licenses/by/4.0/","month":"05","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2026","oa":1,"doi":"10.1016/j.gde.2026.102487","has_accepted_license":"1","PlanS_conform":"1","ddc":["570"],"citation":{"ista":"Varela Martínez I, Pipicelli F, Hippenmeyer S. 2026. Tracing cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics. Current Opinion in Genetics and Development. 99, 102487.","ieee":"I. Varela Martínez, F. Pipicelli, and S. Hippenmeyer, “Tracing cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics,” <i>Current Opinion in Genetics and Development</i>, vol. 99. Elsevier, 2026.","short":"I. Varela Martínez, F. Pipicelli, S. Hippenmeyer, Current Opinion in Genetics and Development 99 (2026).","mla":"Varela Martínez, Irene, et al. “Tracing Cell Lineages in the Developing Brain: Insights from Mosaic Analysis and Clone-Resolved Transcriptomics.” <i>Current Opinion in Genetics and Development</i>, vol. 99, 102487, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102487\">10.1016/j.gde.2026.102487</a>.","ama":"Varela Martínez I, Pipicelli F, Hippenmeyer S. Tracing cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics. <i>Current Opinion in Genetics and Development</i>. 2026;99. doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102487\">10.1016/j.gde.2026.102487</a>","apa":"Varela Martínez, I., Pipicelli, F., &#38; Hippenmeyer, S. (2026). Tracing cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics. <i>Current Opinion in Genetics and Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.gde.2026.102487\">https://doi.org/10.1016/j.gde.2026.102487</a>","chicago":"Varela Martínez, Irene, Fabrizia Pipicelli, and Simon Hippenmeyer. “Tracing Cell Lineages in the Developing Brain: Insights from Mosaic Analysis and Clone-Resolved Transcriptomics.” <i>Current Opinion in Genetics and Development</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.gde.2026.102487\">https://doi.org/10.1016/j.gde.2026.102487</a>."},"quality_controlled":"1","publisher":"Elsevier","intvolume":"        99","department":[{"_id":"SiHi"}],"scopus_import":"1","article_type":"original","_id":"21948","oa_version":"Published Version","article_processing_charge":"Yes (via OA deal)","day":"29","date_created":"2026-06-07T22:01:35Z","external_id":{"pmid":["42214837"]},"title":"Tracing cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics","author":[{"last_name":"Varela Martínez","first_name":"Irene","id":"a69b5985-8829-11f0-8fc2-d0af58f64471","full_name":"Varela Martínez, Irene"},{"full_name":"Pipicelli, Fabrizia","id":"649134fd-d012-11ed-8f82-db1e5050f9ba","last_name":"Pipicelli","first_name":"Fabrizia"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"}],"project":[{"name":"Role of cell lineage in generating cell-type diversity in developing neocortex’","grant_number":"ALTF 994-2023","_id":"7c084566-9f16-11ee-852c-c88a1dbbf1cf"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"}],"abstract":[{"text":"The cerebral cortex comprises diverse neuron and glial cell types generated by radial glial progenitors (RGPs) during development. Although RGPs broadly differentiate according to temporally and spatially regulated molecular logics, the lineage hierarchies linking individual progenitors to defined cell (sub)types are not well understood. Clone-resolved transcriptomics, combining molecular barcoding and single-cell RNA sequencing, allow high-resolution lineage tracing at the single-clone/cell level across different species and models. In this mini-review, we synthesize recent advances in this field, uncovering unexpected lineage relationships in the developing brain, with a particular focus on the cerebral cortex. We further highlight new insights into species-specific differences in the developmental programs generating cell-type diversity, linking changes in clonal architecture to lineage diversification during cortical evolution.","lang":"eng"}],"date_updated":"2026-06-08T07:42:16Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.gde.2026.102487"}],"publication":"Current Opinion in Genetics and Development","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"publication_status":"epub_ahead","article_number":"102487","corr_author":"1","OA_type":"hybrid","date_published":"2026-05-29T00:00:00Z"},{"type":"preprint","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.","status":"public","ec_funded":1,"OA_place":"repository","doi":"10.64898/2026.05.01.722172","has_accepted_license":"1","year":"2026","oa":1,"language":[{"iso":"eng"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)","image":"/images/cc_by_nc.png"},"license":"https://creativecommons.org/licenses/by-nc/4.0/","month":"05","day":"05","_id":"21962","oa_version":"Preprint","article_processing_charge":"No","department":[{"_id":"SiHi"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"MassSpec"},{"_id":"Bio"}],"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.).","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>.","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>","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>","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>."},"ddc":["570"],"OA_type":"green","date_published":"2026-05-05T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"submitted","publication":"bioRxiv","date_updated":"2026-06-16T08:45:25Z","main_file_link":[{"url":"https://doi.org/10.64898/2026.05.01.722172","open_access":"1"}],"abstract":[{"lang":"eng","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."}],"project":[{"call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex","grant_number":"M02416","_id":"264E56E2-B435-11E9-9278-68D0E5697425"},{"grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"date_created":"2026-06-09T08:08:18Z","title":"Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner","author":[{"first_name":"Ana","last_name":"Villalba Requena","orcid":"0000-0002-5615-5277","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","full_name":"Villalba Requena, Ana"},{"full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","last_name":"Beattie","orcid":"0000-0002-8483-8753"},{"orcid":"0000-0002-7462-0048","first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Miranda, Osvaldo","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","orcid":"0000-0001-6618-6889","first_name":"Osvaldo","last_name":"Miranda"},{"full_name":"Krausgruber, Thomas","first_name":"Thomas","last_name":"Krausgruber"},{"last_name":"Senekowitsch","first_name":"Martin","full_name":"Senekowitsch, Martin"},{"last_name":"Farlik","first_name":"Matthias","full_name":"Farlik, Matthias"},{"full_name":"Bock, Christoph","last_name":"Bock","first_name":"Christoph"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061"}]},{"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"}],"main_file_link":[{"url":"https://doi.org/10.64898/2026.05.01.722191","open_access":"1"}],"date_updated":"2026-06-16T08:57:20Z","author":[{"id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","full_name":"Miranda, Osvaldo","orcid":"0000-0001-6618-6889","last_name":"Miranda","first_name":"Osvaldo"},{"first_name":"Ximena","last_name":"Contreras","full_name":"Contreras, Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"id":"70ADC922-B424-11E9-99E3-BA18E6697425","full_name":"Davaatseren, Amarbayasgalan","last_name":"Davaatseren","first_name":"Amarbayasgalan"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207"},{"first_name":"Carmen","last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","full_name":"Villalba Requena, Ana","orcid":"0000-0002-5615-5277","first_name":"Ana","last_name":"Villalba Requena"},{"full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena","last_name":"Heger"},{"full_name":"Marie, Corentine","last_name":"Marie","first_name":"Corentine"},{"full_name":"Hassan, Bassem A.","last_name":"Hassan","first_name":"Bassem A."},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"title":"Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production","date_created":"2026-06-09T08:08:53Z","project":[{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"corr_author":"1","date_published":"2026-05-05T00:00:00Z","OA_type":"green","publication":"bioRxiv","publication_status":"submitted","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"ddc":["570"],"citation":{"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>.","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.).","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>.","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>.","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>","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>"},"article_processing_charge":"No","oa_version":"Preprint","_id":"21963","day":"05","department":[{"_id":"SiHi"},{"_id":"PreCl"},{"_id":"GradSch"}],"month":"05","has_accepted_license":"1","doi":"10.64898/2026.05.01.722191","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)","image":"/images/cc_by_nc.png"},"language":[{"iso":"eng"}],"oa":1,"year":"2026","ec_funded":1,"status":"public","OA_place":"repository","type":"preprint","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."},{"article_number":"101851","date_published":"2025-03-14T00:00:00Z","OA_type":"gold","publication":"eLife","file_date_updated":"2025-04-03T11:19:26Z","pmid":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"In the developing vertebrate central nervous system, neurons and glia typically arise\r\nsequentially from common progenitors. Here, we report that the transcription factor Forkhead\r\nBox G1 (Foxg1) regulates gliogenesis in the mouse neocortex via distinct cell-autonomous roles in progenitors and postmitotic neurons that regulate different aspects of the gliogenic FGF signalling pathway. We demonstrate that loss of Foxg1 in cortical progenitors at neurogenic stages causes premature astrogliogenesis. We identify a novel FOXG1 target, the pro-gliogenic FGF pathway component Fgfr3, which is suppressed by FOXG1 cell-autonomously to maintain neurogenesis. Furthermore, FOXG1 can also suppress premature astrogliogenesis triggered by the augmentation of FGF signalling. We identify a second novel function of FOXG1 in regulating the expression of gliogenic cues in newborn neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons non-autonomously enhances gliogenesis in the progenitors via FGF signalling. These results fit well with the model that newborn neurons secrete cues that trigger progenitors to produce the next wave of cell types, astrocytes. If FGF signalling is attenuated in Foxg1 null progenitors, they progress to oligodendrocyte production. Therefore, loss of FOXG1 transitions the progenitor to a gliogenic state, producing either astrocytes or oligodendrocytes depending on FGF signalling levels. Our results uncover how FOXG1 integrates extrinsic signalling via the FGF pathway to regulate the sequential generation of neurons, astrocytes, and oligodendrocytes in the cerebral cortex. "}],"date_updated":"2025-05-14T11:41:52Z","author":[{"last_name":"Bose","first_name":"Mahima","full_name":"Bose, Mahima"},{"full_name":"Suresh, Varun","first_name":"Varun","last_name":"Suresh"},{"first_name":"Urvi","last_name":"Mishra","full_name":"Mishra, Urvi"},{"last_name":"Talwar","first_name":"Ishita","full_name":"Talwar, Ishita"},{"last_name":"Yadav","first_name":"Anuradha","full_name":"Yadav, Anuradha"},{"last_name":"Biswas","first_name":"Shiona","full_name":"Biswas, Shiona"},{"first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"},{"full_name":"Tole, Shubha","first_name":"Shubha","last_name":"Tole"}],"title":"Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway","external_id":{"pmid":["40085500"]},"date_created":"2023-12-06T13:07:01Z","article_processing_charge":"Yes","oa_version":"Published Version","_id":"14647","day":"14","department":[{"_id":"SiHi"}],"intvolume":"        13","article_type":"original","scopus_import":"1","publisher":"eLife Sciences Publications","ddc":["570"],"quality_controlled":"1","citation":{"chicago":"Bose, Mahima, Varun Suresh, Urvi Mishra, Ishita Talwar, Anuradha Yadav, Shiona Biswas, Simon Hippenmeyer, and Shubha Tole. “Dual Role of FOXG1 in Regulating Gliogenesis in the Developing Neocortex via the FGF Signalling Pathway.” <i>ELife</i>. eLife Sciences Publications, 2025. <a href=\"https://doi.org/10.7554/elife.101851.3\">https://doi.org/10.7554/elife.101851.3</a>.","apa":"Bose, M., Suresh, V., Mishra, U., Talwar, I., Yadav, A., Biswas, S., … Tole, S. (2025). Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.101851.3\">https://doi.org/10.7554/elife.101851.3</a>","ama":"Bose M, Suresh V, Mishra U, et al. Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. <i>eLife</i>. 2025;13. doi:<a href=\"https://doi.org/10.7554/elife.101851.3\">10.7554/elife.101851.3</a>","mla":"Bose, Mahima, et al. “Dual Role of FOXG1 in Regulating Gliogenesis in the Developing Neocortex via the FGF Signalling Pathway.” <i>ELife</i>, vol. 13, 101851, eLife Sciences Publications, 2025, doi:<a href=\"https://doi.org/10.7554/elife.101851.3\">10.7554/elife.101851.3</a>.","short":"M. Bose, V. Suresh, U. Mishra, I. Talwar, A. Yadav, S. Biswas, S. Hippenmeyer, S. Tole, ELife 13 (2025).","ieee":"M. Bose <i>et al.</i>, “Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway,” <i>eLife</i>, vol. 13. eLife Sciences Publications, 2025.","ista":"Bose M, Suresh V, Mishra U, Talwar I, Yadav A, Biswas S, Hippenmeyer S, Tole S. 2025. Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. eLife. 13, 101851."},"has_accepted_license":"1","doi":"10.7554/elife.101851.3","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"language":[{"iso":"eng"}],"file":[{"file_id":"19467","creator":"dernst","success":1,"access_level":"open_access","relation":"main_file","date_created":"2025-04-03T11:19:26Z","file_name":"2025_eLife_Bose.pdf","date_updated":"2025-04-03T11:19:26Z","file_size":17462771,"content_type":"application/pdf","checksum":"64a6a6f86e24b21fe72c7a7fd6056fed"}],"oa":1,"year":"2025","month":"03","type":"journal_article","acknowledgement":"We thank the animal house staff of the Tata Institute of Fundamental Research, Mumbai (TIFR), for their excellent support; Gordon Fishell (Harvard Medical School, USA), and Goichi Miyoshi (Gunma University, Japan) for the Foxg1 floxed mouse line; Hiroshi Kawasaki (Kanazawa University, Japan) for the plasmids pCAG-FGF8 and pCAG-sFgfr3c; Soo Kyung Lee (University at Buffalo, The State University of New York, USA) for the Foxg1lox/lox genotyping primers and protocol. We thank Deepak Modi and Vainav Patel (National Institute for Research in Reproductive and Child Health, NIRRCH, Mumbai, India) for the use of the NIRRCH FACS Facility, and the staff of the NIRRCH and TIFR FACS facilities for their assistance. We thank Denis Jabaudon (University of Geneva, Switzerland) for his critical comments on the manuscript and members of the Jabaudon lab for helpful discussions. This work was funded by the Department of Atomic Energy (DAE), Govt. of India (Project Identification no. RTI4003,\r\nDAE OM no. 1303/2/2019/R&D-II/DAE/2079). ","status":"public","publication_identifier":{"eissn":["2050-084X"]},"OA_place":"publisher","volume":13},{"month":"01","editor":[{"last_name":"Garcia-Marques","first_name":"Jorge","full_name":"Garcia-Marques, Jorge"},{"full_name":"Lee, Tzumin","first_name":"Tzumin","last_name":"Lee"}],"page":"139-151","doi":"10.1007/978-1-0716-4310-5_7","year":"2025","language":[{"iso":"eng"}],"place":"New York, NY","publication_identifier":{"eissn":["1940-6029"],"isbn":["9781071643099"],"issn":["1064-3745"],"eisbn":["9781071643105"]},"ec_funded":1,"status":"public","volume":2886,"series_title":"MIMB","type":"book_chapter","acknowledgement":"We thank all Hippenmeyer lab members for support and discussions. Experimental steps described were optimized with support provided by the Imaging & Optics Facility (IOF) and Preclinical Facility (PCF) at ISTA, Vienna BioCenter Core Facilities (VBCF), and Christoph Bock lab at Center for Molecular Medicine (CeMM). G.C. received funding from European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional funds: The Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H.","date_updated":"2025-04-14T07:43:46Z","abstract":[{"lang":"eng","text":"Mosaic Analysis with Double Markers (MADM) represents a mouse genetic approach coupling differential fluorescent labeling to genetic manipulations in dividing cells and their lineages. MADM uniquely enables the generation and visualization of individual control or homozygous mutant cells in a heterozygous genetic environment. Among its diverse applications, MADM has been used to dissect cell-autonomous gene functions important for cortical development and neural development in general. The high cellular resolution offered by MADM also permits the analysis of transcriptomic changes of individual cells upon genetic manipulations. In this chapter, we describe an experimental protocol combining the generation and isolation of MADM-labeled cells with downstream single-cell RNA-sequencing technologies to probe cell-type specific phenotypes due to genetic mutations at single-cell resolution."}],"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"}],"author":[{"id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T","first_name":"Giselle T","last_name":"Cheung","orcid":"0000-0001-8457-2572"},{"full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","first_name":"Simon"}],"title":"Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM)","external_id":{"pmid":["39745639"]},"date_created":"2025-01-07T08:36:47Z","date_published":"2025-01-03T00:00:00Z","OA_type":"closed access","corr_author":"1","publication_status":"published","pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Lineage Tracing","acknowledged_ssus":[{"_id":"Bio"}],"publisher":"Springer Nature","quality_controlled":"1","citation":{"apa":"Cheung, G. T., Pauler, F., &#38; Hippenmeyer, S. (2025). Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM). In J. Garcia-Marques &#38; T. Lee (Eds.), <i>Lineage Tracing</i> (Vol. 2886, pp. 139–151). New York, NY: Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-4310-5_7\">https://doi.org/10.1007/978-1-0716-4310-5_7</a>","ama":"Cheung GT, Pauler F, Hippenmeyer S. Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM). In: Garcia-Marques J, Lee T, eds. <i>Lineage Tracing</i>. Vol 2886. MIMB. New York, NY: Springer Nature; 2025:139-151. doi:<a href=\"https://doi.org/10.1007/978-1-0716-4310-5_7\">10.1007/978-1-0716-4310-5_7</a>","chicago":"Cheung, Giselle T, Florian Pauler, and Simon Hippenmeyer. “Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM).” In <i>Lineage Tracing</i>, edited by Jorge Garcia-Marques and Tzumin Lee, 2886:139–51. MIMB. New York, NY: Springer Nature, 2025. <a href=\"https://doi.org/10.1007/978-1-0716-4310-5_7\">https://doi.org/10.1007/978-1-0716-4310-5_7</a>.","ista":"Cheung GT, Pauler F, Hippenmeyer S. 2025.Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM). In: Lineage Tracing. Methods in Molecular Biology, vol. 2886, 139–151.","mla":"Cheung, Giselle T., et al. “Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM).” <i>Lineage Tracing</i>, edited by Jorge Garcia-Marques and Tzumin Lee, vol. 2886, Springer Nature, 2025, pp. 139–51, doi:<a href=\"https://doi.org/10.1007/978-1-0716-4310-5_7\">10.1007/978-1-0716-4310-5_7</a>.","short":"G.T. Cheung, F. Pauler, S. Hippenmeyer, in:, J. Garcia-Marques, T. Lee (Eds.), Lineage Tracing, Springer Nature, New York, NY, 2025, pp. 139–151.","ieee":"G. T. Cheung, F. Pauler, and S. Hippenmeyer, “Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM),” in <i>Lineage Tracing</i>, vol. 2886, J. Garcia-Marques and T. Lee, Eds. New York, NY: Springer Nature, 2025, pp. 139–151."},"day":"03","oa_version":"None","article_processing_charge":"No","_id":"18765","scopus_import":"1","department":[{"_id":"SiHi"}],"alternative_title":["Methods in Molecular Biology"],"intvolume":"      2886"},{"month":"05","date_created":"2025-05-20T10:19:29Z","author":[{"last_name":"Varela-Martínez","first_name":"I","full_name":"Varela-Martínez, I"},{"full_name":"Villalba Requena, Ana","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","orcid":"0000-0002-5615-5277","first_name":"Ana","last_name":"Villalba Requena"},{"first_name":"J.","last_name":"Garcia-Marqués","full_name":"Garcia-Marqués, J."},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061"},{"full_name":"Nieto, M.","last_name":"Nieto","first_name":"M."}],"title":"Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis","date_updated":"2025-05-28T06:37:46Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.05.07.652665"}],"abstract":[{"text":"Radial glial progenitors (RGPs) generate all projection neurons (PNs) in the cerebral cortex through incompletely understood processes. Herein, we combine Mosaic Analysis with Double Markers (MADM)-based clonal analysis at embryonic days 12.5 and 13.5 with early postnatal callosal tracing to reveal a lineage progression that challenges the inside-outside model of cortical development and the conventional view of an invariable sequence of asymmetric neurogenic divisions. Our data demonstrate that early multipotent RGPs generate all extra-telencephalic (ET) and intra-telencephalic (IT) PNs across all layers through parallel sublineages and the random specification, during the earliest neurogenic divisions, of fate-restricted daughter RGPs. While the neuronal production of the parental multipotent RGPs consists of small ET-PN or IT-PN outputs, fate-restricted RGPs produce larger translaminar outputs spanning deep and upper layers of only IT-PNs, the predominant mammalian PN subtype. We further show that the emergence of IT-PN fate-restricted RGPs also leads to quantitatively and temporally stereotyped neurogenesis population-wise.","lang":"eng"}],"year":"2025","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"publication_status":"published","publication":"bioRxiv","language":[{"iso":"eng"}],"OA_type":"green","date_published":"2025-05-07T00:00:00Z","doi":"10.1101/2025.05.07.652665","citation":{"ista":"Varela-Martínez I, Villalba Requena A, Garcia-Marqués J, Hippenmeyer S, Nieto M. 2025. Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis. bioRxiv, <a href=\"https://doi.org/10.1101/2025.05.07.652665\">10.1101/2025.05.07.652665</a>.","short":"I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer, M. Nieto, BioRxiv (2025).","mla":"Varela-Martínez, I., et al. “Early Emergence of Projection-Subtype Fate-Restricted Radial Glial Progenitors Orchestrates Neocortical Neurogenesis.” <i>BioRxiv</i>, 2025, doi:<a href=\"https://doi.org/10.1101/2025.05.07.652665\">10.1101/2025.05.07.652665</a>.","ieee":"I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer, and M. Nieto, “Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis,” <i>bioRxiv</i>. 2025.","apa":"Varela-Martínez, I., Villalba Requena, A., Garcia-Marqués, J., Hippenmeyer, S., &#38; Nieto, M. (2025). Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2025.05.07.652665\">https://doi.org/10.1101/2025.05.07.652665</a>","ama":"Varela-Martínez I, Villalba Requena A, Garcia-Marqués J, Hippenmeyer S, Nieto M. Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis. <i>bioRxiv</i>. 2025. doi:<a href=\"https://doi.org/10.1101/2025.05.07.652665\">10.1101/2025.05.07.652665</a>","chicago":"Varela-Martínez, I, Ana Villalba Requena, J. Garcia-Marqués, Simon Hippenmeyer, and M. Nieto. “Early Emergence of Projection-Subtype Fate-Restricted Radial Glial Progenitors Orchestrates Neocortical Neurogenesis.” <i>BioRxiv</i>, 2025. <a href=\"https://doi.org/10.1101/2025.05.07.652665\">https://doi.org/10.1101/2025.05.07.652665</a>."},"OA_place":"repository","status":"public","department":[{"_id":"SiHi"}],"acknowledgement":"We thank M. Caouyette for the plasmid construction for Pou3f1 overexpression; C. Varela747 Martínez for help with the code for graphical analysis; all members from the Nieto’s lab for\r\ncomment on the manuscript, specially to F. Martín for the insightful discussions;J.C. Oliveros\r\nand J.A. García from the computational service of the CNB for help with the analysis of\r\nRNAseq dataset, C.O. Sorzano for the help with statistical analysis, and the service of\r\nAdvance Optical Microscopy of the CNB for their technical advice.\r\nI.V.M holds a fellowship funded by MCICIU (PRE-2018-083376), the work was funded by\r\nPID2020-112831GB-I00 funded by MCIN/AEI /10.13039/501100011033.\r\n","day":"07","type":"preprint","_id":"19717","oa_version":"Preprint","article_processing_charge":"No"},{"_id":"8616","article_processing_charge":"Yes","oa_version":"Published Version","day":"01","intvolume":"        16","department":[{"_id":"SiHi"}],"scopus_import":"1","article_type":"original","publisher":"Springer Nature","ddc":["570"],"quality_controlled":"1","citation":{"chicago":"Gao, Xiaofei, Jun-Liszt Li, Xingjun Chen, Bo Ci, Fei Chen, Nannan Lu, Bo Shen, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” <i>Nature Communications</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41467-025-60308-0\">https://doi.org/10.1038/s41467-025-60308-0</a>.","ama":"Gao X, Li J-L, Chen X, et al. Reduction of neuronal activity mediated by blood-vessel regression in the brain. <i>Nature Communications</i>. 2025;16. doi:<a href=\"https://doi.org/10.1038/s41467-025-60308-0\">10.1038/s41467-025-60308-0</a>","apa":"Gao, X., Li, J.-L., Chen, X., Ci, B., Chen, F., Lu, N., … Ge, W. (2025). Reduction of neuronal activity mediated by blood-vessel regression in the brain. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-025-60308-0\">https://doi.org/10.1038/s41467-025-60308-0</a>","mla":"Gao, Xiaofei, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” <i>Nature Communications</i>, vol. 16, 5840, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41467-025-60308-0\">10.1038/s41467-025-60308-0</a>.","short":"X. Gao, J.-L. Li, X. Chen, B. Ci, F. Chen, N. Lu, B. Shen, L. Zheng, J.-M. Jia, Y. Yi, S. Zhang, Y.-C. Shi, K. Shi, N.E. Propson, Y. Huang, K. Poinsatte, Z. Zhang, Y. Yue, D.B. Bosco, Y. Lu, S. Yang, R.H. Adams, V. Lindner, F. Huang, L.-J. Wu, H. Zheng, F. Han, S. Hippenmeyer, A.M. Stowe, B. Peng, M. Margeta, X. Wang, Q. Liu, J. Körbelin, M. Trepel, H. Lu, B.O. Zhou, H. Zhao, W. Su, R.M. Bachoo, W. Ge, Nature Communications 16 (2025).","ieee":"X. Gao <i>et al.</i>, “Reduction of neuronal activity mediated by blood-vessel regression in the brain,” <i>Nature Communications</i>, vol. 16. Springer Nature, 2025.","ista":"Gao X, Li J-L, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J-M, Yi Y, Zhang S, Shi Y-C, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco DB, Lu Y, Yang S, Adams RH, Lindner V, Huang F, Wu L-J, Zheng H, Han F, Hippenmeyer S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Körbelin J, Trepel M, Lu H, Zhou BO, Zhao H, Su W, Bachoo RM, Ge W. 2025. Reduction of neuronal activity mediated by blood-vessel regression in the brain. Nature Communications. 16, 5840."},"article_number":"5840","OA_type":"gold","date_published":"2025-07-01T00:00:00Z","publication":"Nature Communications","file_date_updated":"2025-07-07T09:52:46Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"published","abstract":[{"lang":"eng","text":"The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain."}],"date_updated":"2025-09-04T07:08:37Z","date_created":"2020-10-06T08:58:59Z","external_id":{"isi":["001523450500035"]},"author":[{"first_name":"Xiaofei","last_name":"Gao","full_name":"Gao, Xiaofei"},{"full_name":"Li, Jun-Liszt","first_name":"Jun-Liszt","last_name":"Li"},{"first_name":"Xingjun","last_name":"Chen","full_name":"Chen, Xingjun"},{"full_name":"Ci, Bo","first_name":"Bo","last_name":"Ci"},{"full_name":"Chen, Fei","first_name":"Fei","last_name":"Chen"},{"full_name":"Lu, Nannan","last_name":"Lu","first_name":"Nannan"},{"full_name":"Shen, Bo","first_name":"Bo","last_name":"Shen"},{"first_name":"Lijun","last_name":"Zheng","full_name":"Zheng, Lijun"},{"last_name":"Jia","first_name":"Jie-Min","full_name":"Jia, Jie-Min"},{"full_name":"Yi, Yating","first_name":"Yating","last_name":"Yi"},{"last_name":"Zhang","first_name":"Shiwen","full_name":"Zhang, Shiwen"},{"full_name":"Shi, Ying-Chao","first_name":"Ying-Chao","last_name":"Shi"},{"full_name":"Shi, Kaibin","first_name":"Kaibin","last_name":"Shi"},{"last_name":"Propson","first_name":"Nicholas E","full_name":"Propson, Nicholas E"},{"first_name":"Yubin","last_name":"Huang","full_name":"Huang, Yubin"},{"first_name":"Katherine","last_name":"Poinsatte","full_name":"Poinsatte, Katherine"},{"last_name":"Zhang","first_name":"Zhaohuan","full_name":"Zhang, Zhaohuan"},{"full_name":"Yue, Yuanlei","first_name":"Yuanlei","last_name":"Yue"},{"first_name":"Dale B","last_name":"Bosco","full_name":"Bosco, Dale B"},{"last_name":"Lu","first_name":"Ying-mei","full_name":"Lu, Ying-mei"},{"first_name":"Shi-bing","last_name":"Yang","full_name":"Yang, Shi-bing"},{"first_name":"Ralf H.","last_name":"Adams","full_name":"Adams, Ralf H."},{"full_name":"Lindner, Volkhard","last_name":"Lindner","first_name":"Volkhard"},{"full_name":"Huang, Fen","last_name":"Huang","first_name":"Fen"},{"last_name":"Wu","first_name":"Long-Jun","full_name":"Wu, Long-Jun"},{"full_name":"Zheng, Hui","first_name":"Hui","last_name":"Zheng"},{"last_name":"Han","first_name":"Feng","full_name":"Han, Feng"},{"last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"},{"full_name":"Stowe, Ann M.","last_name":"Stowe","first_name":"Ann M."},{"full_name":"Peng, Bo","first_name":"Bo","last_name":"Peng"},{"first_name":"Marta","last_name":"Margeta","full_name":"Margeta, Marta"},{"full_name":"Wang, Xiaoqun","first_name":"Xiaoqun","last_name":"Wang"},{"full_name":"Liu, Qiang","last_name":"Liu","first_name":"Qiang"},{"first_name":"Jakob","last_name":"Körbelin","full_name":"Körbelin, Jakob"},{"full_name":"Trepel, Martin","first_name":"Martin","last_name":"Trepel"},{"last_name":"Lu","first_name":"Hui","full_name":"Lu, Hui"},{"first_name":"Bo O.","last_name":"Zhou","full_name":"Zhou, Bo O."},{"last_name":"Zhao","first_name":"Hu","full_name":"Zhao, Hu"},{"full_name":"Su, Wenzhi","first_name":"Wenzhi","last_name":"Su"},{"full_name":"Bachoo, Robert M.","first_name":"Robert M.","last_name":"Bachoo"},{"full_name":"Ge, Woo-ping","last_name":"Ge","first_name":"Woo-ping"}],"title":"Reduction of neuronal activity mediated by blood-vessel regression in the brain","project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020"}],"type":"journal_article","acknowledgement":"The project was initiated in the Jan lab at UCSF. We thank Lily Jan and Yuh-Nung Jan’s generous support. We thank Liqun Luo’s lab for providing MADM-7 mice and Rolf A Brekken for VEGF-antibodies.  Drs. Yuanquan Song (UPenn), Zhaozhu Hu (JHU), Ji Hu (ShanghaiTech), Yang Xiang (U. Mass), Hao Wang (Zhejiang U.) and Ruikang Wang (U. Washington) for critical input, colleagues at Children’s Research Institute, Departments of Neuroscience, Neurology and Neurotherapeutics, Pediatrics from UT Southwestern, and colleagues from the Jan lab for discussion. Dr. Bridget Samuels, Sean Morrison (UT Southwestern), and Nannan Lu (Zhejiang U.) for critical reading. We acknowledge the assistance of the CIBR Imaging core. We also thank UT Southwestern Live Cell Imaging Facility, a Shared Resource of the Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support Grant, P30 CA142543K. This work is supported by CIBR funds and the American Heart Association AWRP Summer 2016 Innovative Research Grant (17IRG33410377) to W-P.G.; National Natural Science Foundation of China (No.81370031) to Z.Z.;National Key Research and Development Program of China (2016YFE0125400)to F.H.;National Natural Science Foundations of China (No. 81473202) to Y.L.; National Natural Science Foundation of China (No.31600839) and Shenzhen Science and Technology Research Program (JCYJ20170818163320865) to B.P.; National Natural Science Foundation of China (No. 31800864) and Westlake University start-up funds to J-M. J. NIH R01NS088627 to W.L.J.; NIH: R01 AG020670 and RF1AG054111 to H.Z.; R01 NS088555 to A.M.S., and European Research Council No.725780 to S.H.;W-P.G. was a recipient of Bugher-American Heart Association Dan Adams Thinking Outside the Box Award.","status":"public","ec_funded":1,"publication_identifier":{"eissn":["2041-1723"]},"volume":16,"OA_place":"publisher","doi":"10.1038/s41467-025-60308-0","has_accepted_license":"1","language":[{"iso":"eng"}],"file":[{"creator":"dernst","success":1,"access_level":"open_access","file_id":"19971","file_name":"2025_NatureComm_Gao.pdf","date_updated":"2025-07-07T09:52:46Z","content_type":"application/pdf","file_size":17018106,"checksum":"f59748cb67232cfb210035d9aef60836","relation":"main_file","date_created":"2025-07-07T09:52:46Z"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"year":"2025","oa":1,"DOAJ_listed":"1","isi":1,"month":"07"},{"publication_identifier":{"issn":["0959-4388"]},"status":"public","OA_place":"publisher","volume":93,"type":"journal_article","acknowledgement":"We wish to thank all members of the Hippenmeyer laboratory at ISTA for exciting discussions on the subject of this review. We apologize to colleagues whose work we could not cite and/or discuss in the frame of the available space. Work in the Hippenmeyer laboratory on the discussed topic is supported by ISTA institutional funds, an EMBO LTF (ALTF 994–2023) to F.P, and FWF SFB F78 to S.H.","isi":1,"month":"08","PlanS_conform":"1","has_accepted_license":"1","doi":"10.1016/j.conb.2025.103046","oa":1,"year":"2025","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"creator":"dernst","success":1,"access_level":"open_access","file_id":"20894","file_name":"2025_CurrentOpNeurobiology_Pipicelli.pdf","date_updated":"2025-12-30T08:25:49Z","file_size":1592649,"checksum":"05bacb4acbe6275d43e873dec9ba1d52","content_type":"application/pdf","relation":"main_file","date_created":"2025-12-30T08:25:49Z"}],"language":[{"iso":"eng"}],"publisher":"Elsevier","quality_controlled":"1","citation":{"ista":"Pipicelli F, Villalba Requena A, Hippenmeyer S. 2025. How radial glia progenitor lineages generate cell-type diversity in the developing cerebral cortex. Current Opinion in Neurobiology. 93, 103046.","mla":"Pipicelli, Fabrizia, et al. “How Radial Glia Progenitor Lineages Generate Cell-Type Diversity in the Developing Cerebral Cortex.” <i>Current Opinion in Neurobiology</i>, vol. 93, 103046, Elsevier, 2025, doi:<a href=\"https://doi.org/10.1016/j.conb.2025.103046\">10.1016/j.conb.2025.103046</a>.","short":"F. Pipicelli, A. Villalba Requena, S. Hippenmeyer, Current Opinion in Neurobiology 93 (2025).","ieee":"F. Pipicelli, A. Villalba Requena, and S. Hippenmeyer, “How radial glia progenitor lineages generate cell-type diversity in the developing cerebral cortex,” <i>Current Opinion in Neurobiology</i>, vol. 93. Elsevier, 2025.","ama":"Pipicelli F, Villalba Requena A, Hippenmeyer S. How radial glia progenitor lineages generate cell-type diversity in the developing cerebral cortex. <i>Current Opinion in Neurobiology</i>. 2025;93. doi:<a href=\"https://doi.org/10.1016/j.conb.2025.103046\">10.1016/j.conb.2025.103046</a>","apa":"Pipicelli, F., Villalba Requena, A., &#38; Hippenmeyer, S. (2025). How radial glia progenitor lineages generate cell-type diversity in the developing cerebral cortex. <i>Current Opinion in Neurobiology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.conb.2025.103046\">https://doi.org/10.1016/j.conb.2025.103046</a>","chicago":"Pipicelli, Fabrizia, Ana Villalba Requena, and Simon Hippenmeyer. “How Radial Glia Progenitor Lineages Generate Cell-Type Diversity in the Developing Cerebral Cortex.” <i>Current Opinion in Neurobiology</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.conb.2025.103046\">https://doi.org/10.1016/j.conb.2025.103046</a>."},"ddc":["570"],"day":"01","article_processing_charge":"Yes (via OA deal)","oa_version":"Published Version","_id":"19718","article_type":"original","scopus_import":"1","department":[{"_id":"SiHi"}],"intvolume":"        93","date_updated":"2025-12-30T10:54:14Z","abstract":[{"text":"The cerebral cortex is arguably the most complex organ in humans. The cortical architecture is characterized by a remarkable diversity of neuronal and glial cell types that make up its neuronal circuits. Following a precise temporally ordered program, radial glia progenitor (RGP) cells generate all cortical excitatory projection neurons and glial cell-types. Cortical excitatory projection neurons are produced either directly or via intermediate progenitors, through indirect neurogenesis. How the extensive cortical cell-type diversity is generated during cortex development remains, however, a fundamental open question. How do RGPs quantitatively and qualitatively generate all the neocortical neurons? How does direct and indirect neurogenesis contribute to the establishment of neuronal and lineage heterogeneity? Whether RGPs represent a homogeneous and/or multipotent progenitor population, or if RGPs consist of heterogeneous groups is currently also not known. In this review, we will summarize the latest findings that contributed to a deeper insight into the above key questions.","lang":"eng"}],"project":[{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"},{"_id":"7c084566-9f16-11ee-852c-c88a1dbbf1cf","name":"Role of cell lineage in generating cell-type diversity in developing neocortex’","grant_number":"ALTF 994-2023"}],"author":[{"id":"649134fd-d012-11ed-8f82-db1e5050f9ba","full_name":"Pipicelli, Fabrizia","first_name":"Fabrizia","last_name":"Pipicelli"},{"id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","full_name":"Villalba Requena, Ana","last_name":"Villalba Requena","first_name":"Ana","orcid":"0000-0002-5615-5277"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"title":"How radial glia progenitor lineages generate cell-type diversity in the developing cerebral cortex","date_created":"2025-05-20T10:20:09Z","external_id":{"isi":["001496227000001"],"pmid":["40383049"]},"date_published":"2025-08-01T00:00:00Z","OA_type":"hybrid","corr_author":"1","article_number":"103046","pmid":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Current Opinion in Neurobiology","file_date_updated":"2025-12-30T08:25:49Z"},{"article_processing_charge":"No","oa_version":"Preprint","_id":"19762","type":"preprint","day":"23","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).","department":[{"_id":"SiHi"}],"status":"public","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>","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.).","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>.","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>."},"OA_place":"repository","doi":"10.1101/2025.05.22.655488","date_published":"2025-05-23T00:00:00Z","OA_type":"green","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"language":[{"iso":"eng"}],"publication":"bioRxiv","oa":1,"publication_status":"submitted","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2025","abstract":[{"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.","lang":"eng"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.05.22.655488"}],"date_updated":"2025-12-30T10:54:12Z","title":"Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development","author":[{"last_name":"Cárdenas","first_name":"Adrián","full_name":"Cárdenas, Adrián"},{"first_name":"Irem","last_name":"Çelik","full_name":"Çelik, Irem"},{"first_name":"Alexandre","last_name":"Espinós","full_name":"Espinós, Alexandre"},{"first_name":"Carmen","last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"López-González, Lara","first_name":"Lara","last_name":"López-González"},{"last_name":"del-Valle-Anton","first_name":"Lucia","full_name":"del-Valle-Anton, Lucia"},{"last_name":"Fernández","first_name":"Virginia","full_name":"Fernández, Virginia"},{"full_name":"Amin, Salma","first_name":"Salma","last_name":"Amin"},{"full_name":"Negri, Enrico","first_name":"Enrico","last_name":"Negri"},{"full_name":"Ortuño, Eduardo Fernández","last_name":"Ortuño","first_name":"Eduardo Fernández"},{"last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"},{"last_name":"Borrell","first_name":"Víctor","full_name":"Borrell, Víctor"}],"date_created":"2025-05-29T10:45:55Z","month":"05","project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}]},{"ddc":["570"],"quality_controlled":"1","citation":{"apa":"Hansen, A. H., &#38; Hippenmeyer, S. (2024). Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2023.102795\">https://doi.org/10.1016/j.xpro.2023.102795</a>","ama":"Hansen AH, Hippenmeyer S. Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. <i>STAR Protocols</i>. 2024;5(1). doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102795\">10.1016/j.xpro.2023.102795</a>","chicago":"Hansen, Andi H, and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2023.102795\">https://doi.org/10.1016/j.xpro.2023.102795</a>.","ista":"Hansen AH, Hippenmeyer S. 2024. Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. STAR Protocols. 5(1), 102795.","ieee":"A. H. Hansen and S. Hippenmeyer, “Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers,” <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2024.","short":"A.H. Hansen, S. Hippenmeyer, STAR Protocols 5 (2024).","mla":"Hansen, Andi H., and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>, vol. 5, no. 1, 102795, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102795\">10.1016/j.xpro.2023.102795</a>."},"publisher":"Elsevier","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"department":[{"_id":"SiHi"}],"intvolume":"         5","article_type":"review","scopus_import":"1","article_processing_charge":"Yes","oa_version":"Published Version","_id":"14794","day":"15","title":"Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers","author":[{"last_name":"Hansen","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"}],"external_id":{"pmid":["38165800"]},"date_created":"2024-01-14T23:00:56Z","project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular mechanisms of radial neuronal migration"}],"abstract":[{"text":"Mosaic analysis with double markers (MADM) technology enables the sparse labeling of genetically defined neurons. We present a protocol for time-lapse imaging of cortical projection neuron migration in mice using MADM. We describe steps for the isolation, culturing, and 4D imaging of neuronal dynamics in MADM-labeled brain tissue. While this protocol is compatible with other single-cell labeling methods, the MADM approach provides a genetic platform for the functional assessment of cell-autonomous candidate gene function and the relative contribution of non-cell-autonomous effects.\r\n\r\nFor complete details on the use and execution of this protocol, please refer to Hansen et al. (2022),1 Contreras et al. (2021),2 and Amberg and Hippenmeyer (2021).3","lang":"eng"}],"date_updated":"2025-04-15T07:32:40Z","file_date_updated":"2024-07-16T12:04:46Z","publication":"STAR Protocols","pmid":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","article_number":"102795","date_published":"2024-03-15T00:00:00Z","volume":5,"status":"public","publication_identifier":{"eissn":["2666-1667"]},"acknowledgement":"We thank Florian Pauler for discussion and his expert technical support. This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging and Optics Facility (IOF) and Preclinical Facility (PCF). A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences.","type":"journal_article","month":"03","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"language":[{"iso":"eng"}],"file":[{"relation":"main_file","date_created":"2024-07-16T12:04:46Z","file_name":"2024_STARProtoc_Hansen.pdf","date_updated":"2024-07-16T12:04:46Z","checksum":"4644d537451c5c114a9d7c7829b65bba","file_size":3758943,"content_type":"application/pdf","file_id":"17264","creator":"dernst","success":1,"access_level":"open_access"}],"oa":1,"year":"2024","has_accepted_license":"1","related_material":{"link":[{"url":"http://github.com/hippenmeyerlab","relation":"software"}]},"issue":"1","doi":"10.1016/j.xpro.2023.102795"},{"quality_controlled":"1","citation":{"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.","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.","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>.","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.","apa":"Cheung, G. T., Pauler, F., Koppensteiner, P., Krausgruber, T., Streicher, C., Schrammel, M., … Hippenmeyer, S. (2024). Multipotent progenitors instruct ontogeny of the superior colliculus. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">https://doi.org/10.1016/j.neuron.2023.11.009</a>","ama":"Cheung GT, Pauler F, Koppensteiner P, et al. Multipotent progenitors instruct ontogeny of the superior colliculus. <i>Neuron</i>. 2024;112(2):230-246.e11. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">10.1016/j.neuron.2023.11.009</a>","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>."},"ddc":["570"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"PreCl"}],"publisher":"Elsevier","scopus_import":"1","article_type":"original","intvolume":"       112","department":[{"_id":"SiHi"},{"_id":"RySh"}],"day":"17","_id":"12875","oa_version":"Published Version","article_processing_charge":"Yes (via OA deal)","project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805"}],"external_id":{"pmid":["38096816"],"isi":["001163937900001"]},"date_created":"2023-04-27T09:41:48Z","author":[{"id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572","last_name":"Cheung","first_name":"Giselle T"},{"first_name":"Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner"},{"last_name":"Krausgruber","first_name":"Thomas","full_name":"Krausgruber, Thomas"},{"full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen"},{"full_name":"Schrammel, Martin","id":"f13e7cae-e8bd-11ed-841a-96dedf69f46d","first_name":"Martin","last_name":"Schrammel"},{"full_name":"Özgen, Natalie Y","id":"e68ece33-f6e0-11ea-865d-ae1031dcc090","last_name":"Özgen","first_name":"Natalie Y"},{"id":"1d144691-e8be-11ed-9b33-bdd3077fad4c","full_name":"Ivec, Alexis","last_name":"Ivec","first_name":"Alexis"},{"last_name":"Bock","first_name":"Christoph","full_name":"Bock, Christoph"},{"last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"title":"Multipotent progenitors instruct ontogeny of the superior colliculus","date_updated":"2025-12-30T10:54:12Z","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"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"published","pmid":1,"publication":"Neuron","file_date_updated":"2024-02-06T13:56:15Z","date_published":"2024-01-17T00:00:00Z","corr_author":"1","volume":112,"publication_identifier":{"issn":["0896-6273"]},"status":"public","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. ","type":"journal_article","month":"01","isi":1,"year":"2024","oa":1,"file":[{"file_id":"14944","access_level":"open_access","creator":"dernst","success":1,"date_created":"2024-02-06T13:56:15Z","relation":"main_file","date_updated":"2024-02-06T13:56:15Z","file_name":"2024_Neuron_Cheung.pdf","content_type":"application/pdf","checksum":"32b3788f7085cf44a84108d8faaff3ce","file_size":5942467}],"language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"doi":"10.1016/j.neuron.2023.11.009","issue":"2","related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-pedigree-of-brain-cells/","description":"News on ISTA Website","relation":"press_release"}]},"has_accepted_license":"1","page":"230-246.e11"},{"external_id":{"pmid":["38070137"]},"date_created":"2023-12-13T11:48:05Z","title":"Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry","author":[{"full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207"},{"last_name":"Cheung","first_name":"Giselle T","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061"}],"project":[{"_id":"268F8446-B435-11E9-9278-68D0E5697425","name":"Role of Eed in neural stem cell lineage progression","grant_number":"T01031","call_identifier":"FWF"},{"call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020"}],"abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.\r\nFor complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1"}],"date_updated":"2025-04-15T08:23:06Z","file_date_updated":"2024-07-16T11:50:03Z","publication":"STAR Protocols","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"published","pmid":1,"article_number":"102771","corr_author":"1","date_published":"2024-03-15T00:00:00Z","ddc":["570"],"citation":{"chicago":"Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>.","ama":"Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. 2024;5(1). doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>","apa":"Amberg, N., Cheung, G. T., &#38; Hippenmeyer, S. (2024). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>","mla":"Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>, vol. 5, no. 1, 102771, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>.","short":"N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2024).","ieee":"N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry,” <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2024.","ista":"Amberg N, Cheung GT, Hippenmeyer S. 2024. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 5(1), 102771."},"quality_controlled":"1","publisher":"Elsevier","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"intvolume":"         5","department":[{"_id":"SiHi"}],"scopus_import":"1","article_type":"review","_id":"14683","oa_version":"Published Version","article_processing_charge":"Yes (in subscription journal)","day":"15","month":"03","language":[{"iso":"eng"}],"file":[{"file_id":"17260","creator":"dernst","success":1,"access_level":"open_access","relation":"main_file","date_created":"2024-07-16T11:50:03Z","date_updated":"2024-07-16T11:50:03Z","file_name":"2024_STARProtoc_Amberg.pdf","checksum":"3f0ee62e04bf5a44b45b035662826e95","file_size":8871807,"content_type":"application/pdf"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2024","oa":1,"doi":"10.1016/j.xpro.2023.102771","issue":"1","has_accepted_license":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"volume":5,"status":"public","ec_funded":1,"publication_identifier":{"issn":["2666-1667"]},"acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging & Optics Facility (IOF) and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme (T 1031). G.C. received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411 as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","type":"journal_article"},{"oa":1,"year":"2024","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"file":[{"file_id":"18809","access_level":"open_access","creator":"dernst","success":1,"date_created":"2025-01-09T12:12:40Z","relation":"main_file","date_updated":"2025-01-09T12:12:40Z","file_name":"2024_STARProtoc_Cheung.pdf","file_size":5186071,"checksum":"d8a8cdba82a394e731aa699ace1ae433","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"has_accepted_license":"1","doi":"10.1016/j.xpro.2024.103157","issue":"3","month":"09","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).","APC_amount":"804 EUR","type":"journal_article","OA_place":"publisher","volume":5,"publication_identifier":{"eissn":["2666-1667"]},"ec_funded":1,"status":"public","publication_status":"published","pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"STAR Protocols","file_date_updated":"2025-01-09T12:12:40Z","date_published":"2024-09-20T00:00:00Z","OA_type":"gold","corr_author":"1","article_number":"103157","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"author":[{"full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8457-2572","first_name":"Giselle T","last_name":"Cheung"},{"last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"}],"title":"Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice","external_id":{"pmid":["38935508"]},"date_created":"2024-06-30T22:01:04Z","date_updated":"2025-12-30T10:54:11Z","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"}],"article_type":"original","scopus_import":"1","department":[{"_id":"SiHi"}],"intvolume":"         5","day":"20","article_processing_charge":"Yes","oa_version":"Published Version","_id":"17187","citation":{"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.","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>.","short":"G.T. Cheung, C. Streicher, S. Hippenmeyer, STAR Protocols 5 (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>","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>"},"quality_controlled":"1","ddc":["570"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"publisher":"Elsevier"},{"day":"20","_id":"17232","article_processing_charge":"Yes","oa_version":"Published Version","scopus_import":"1","article_type":"original","intvolume":"         5","department":[{"_id":"SiHi"},{"_id":"PreCl"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"PreCl"}],"publisher":"Elsevier","quality_controlled":"1","citation":{"ista":"Cheung GT, Pauler F, Koppensteiner P, Hippenmeyer S. 2024. Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. STAR Protocols. 5(3), 103168.","ieee":"G. T. Cheung, F. Pauler, P. Koppensteiner, and S. Hippenmeyer, “Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq,” <i>STAR Protocols</i>, vol. 5, no. 3. Elsevier, 2024.","short":"G.T. Cheung, F. Pauler, P. Koppensteiner, S. Hippenmeyer, STAR Protocols 5 (2024).","mla":"Cheung, Giselle T., et al. “Protocol for Mapping Cell Lineage and Cell-Type Identity of Clonally-Related Cells in Situ Using MADM-CloneSeq.” <i>STAR Protocols</i>, vol. 5, no. 3, 103168, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">10.1016/j.xpro.2024.103168</a>.","apa":"Cheung, G. T., Pauler, F., Koppensteiner, P., &#38; Hippenmeyer, S. (2024). Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">https://doi.org/10.1016/j.xpro.2024.103168</a>","ama":"Cheung GT, Pauler F, Koppensteiner P, Hippenmeyer S. Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. <i>STAR Protocols</i>. 2024;5(3). doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">10.1016/j.xpro.2024.103168</a>","chicago":"Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, and Simon Hippenmeyer. “Protocol for Mapping Cell Lineage and Cell-Type Identity of Clonally-Related Cells in Situ Using MADM-CloneSeq.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">https://doi.org/10.1016/j.xpro.2024.103168</a>."},"ddc":["570"],"OA_type":"gold","date_published":"2024-09-20T00:00:00Z","article_number":"103168","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"publication_status":"published","file_date_updated":"2025-01-09T12:16:53Z","publication":"STAR Protocols","date_updated":"2025-12-30T10:54:12Z","abstract":[{"lang":"eng","text":"The lineage relationship of clonally-related cells offers important insights into the ontogeny and cytoarchitecture of the brain in health and disease. Here, we provide a protocol to concurrently assess cell lineage relationship and cell-type identity among clonally-related cells in situ. We first describe the preparation and screening of acute brain slices containing clonally-related cells labeled using mosaic analysis with double markers (MADM). We then outline steps to collect RNA from individual cells for downstream applications and cell-type identification using RNA sequencing.\r\nFor complete details on the use and execution of this protocol, please refer to Cheung et al.\r\n1"}],"project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"external_id":{"pmid":["38968076"]},"date_created":"2024-07-14T22:01:10Z","author":[{"last_name":"Cheung","first_name":"Giselle T","orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T"},{"first_name":"Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"title":"Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq","type":"journal_article","APC_amount":"804 EUR","acknowledgement":"We thank R. Beattie and T. Asenov for designing and producing components of the multi-well slice recover chamber. We thank R. Shigemoto for providing equipment access. We thank C. Streicher and A. Heger for mouse breeding support. This work was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging & Optics, Miba Machine Shop, and Preclinical facilities. G.C. received funding from the European Commission (IST plus postdoctoral fellowship) and S.H. was funded by ISTA institutional funds and the Austrian Science Fund Special Research Programmes (FWF SFB-F78 Neuro Stem Modulation).","publication_identifier":{"eissn":["2666-1667"]},"status":"public","volume":5,"OA_place":"publisher","issue":"3","doi":"10.1016/j.xpro.2024.103168","has_accepted_license":"1","year":"2024","oa":1,"language":[{"iso":"eng"}],"file":[{"file_id":"18810","access_level":"open_access","creator":"dernst","success":1,"date_created":"2025-01-09T12:16:53Z","relation":"main_file","file_name":"2024_STARProtoc_Cheung2.pdf","date_updated":"2025-01-09T12:16:53Z","checksum":"464f52ecc6ec92f509552823bb82bf79","file_size":6445556,"content_type":"application/pdf"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"month":"09"},{"language":[{"iso":"eng"}],"year":"2024","related_material":{"record":[{"id":"20212","status":"public","relation":"dissertation_contains"}]},"page":"283-299","doi":"10.1007/978-1-0716-3969-6_19","editor":[{"full_name":"Toyooka, Kazuhito","first_name":"Kazuhito","last_name":"Toyooka"}],"month":"08","edition":"1","acknowledgement":"We thank all Hippenmeyer lab members for support and discussions. This work was supported by the Scientific Service Units (SSU) at ISTA through resources provided by the Imaging & Optics Facility (IOF). O.A.M was a recipient of a DOC Fellowship (26253) of the Austrian Academy of Sciences. This work was supported by ISTA institutional funds, and The Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H.","type":"book_chapter","series_title":"MIMB","volume":2831,"status":"public","place":"New York, NY","publication_identifier":{"eissn":["1940-6029"],"issn":["1064-3745"],"isbn":["9781071639689"],"eisbn":["9781071639696"]},"publication":"Neuronal Morphogenesis","pmid":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","date_published":"2024-08-13T00:00:00Z","title":"Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers","author":[{"first_name":"Osvaldo","last_name":"Miranda","orcid":"0000-0001-6618-6889","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","full_name":"Miranda, Osvaldo"},{"first_name":"Giselle T","last_name":"Cheung","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"date_created":"2024-08-13T12:16:41Z","external_id":{"pmid":["39134857"]},"project":[{"_id":"34c9fbcb-11ca-11ed-8bc3-98fa5658610d","name":"Molecular Mechanisms Regulating Cortical Neural Stem Cell Lineage Progression and Astrocyte Development","grant_number":"26253"},{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"abstract":[{"lang":"eng","text":"Mosaic Analysis with Double Markers (MADM) is a powerful genetic method typically used for lineage tracing and to disentangle cell autonomous and tissue-wide roles of candidate genes with single cell resolution. Given the relatively sparse labeling, depending on which of the 19 MADM chromosomes one chooses, the MADM approach represents the perfect opportunity for cell morphology analysis. Various MADM studies include reports of morphological anomalies and phenotypes in the central nervous system (CNS). MADM for any candidate gene can easily incorporate morphological analysis within the experimental workflow. Here, we describe the methods of morphological cell analysis which we developed in the course of diverse recent MADM studies. This chapter will specifically focus on methods to quantify aspects of the morphology of neurons and astrocytes within the CNS, but these methods can broadly be applied to any MADM-labeled cells throughout the entire organism. We will cover two analyses—soma volume and dendrite characterization—of physical characteristics of pyramidal neurons in the somatosensory cortex, and two analyses—volume and Sholl analysis—of astrocyte morphology."}],"date_updated":"2026-04-07T12:32:35Z","alternative_title":["Methods in Molecular Biology"],"department":[{"_id":"GradSch"},{"_id":"SiHi"}],"intvolume":"      2831","scopus_import":"1","article_processing_charge":"No","oa_version":"None","_id":"17425","day":"13","quality_controlled":"1","citation":{"apa":"Miranda, O., Cheung, G. T., &#38; Hippenmeyer, S. (2024). Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers. In K. Toyooka (Ed.), <i>Neuronal Morphogenesis</i> (1st ed., Vol. 2831, pp. 283–299). New York, NY: Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-3969-6_19\">https://doi.org/10.1007/978-1-0716-3969-6_19</a>","ama":"Miranda O, Cheung GT, Hippenmeyer S. Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers. In: Toyooka K, ed. <i>Neuronal Morphogenesis</i>. Vol 2831. 1st ed. MIMB. New York, NY: Springer Nature; 2024:283-299. doi:<a href=\"https://doi.org/10.1007/978-1-0716-3969-6_19\">10.1007/978-1-0716-3969-6_19</a>","chicago":"Miranda, Osvaldo, Giselle T Cheung, and Simon Hippenmeyer. “Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers.” In <i>Neuronal Morphogenesis</i>, edited by Kazuhito Toyooka, 1st ed., 2831:283–99. MIMB. New York, NY: Springer Nature, 2024. <a href=\"https://doi.org/10.1007/978-1-0716-3969-6_19\">https://doi.org/10.1007/978-1-0716-3969-6_19</a>.","ista":"Miranda O, Cheung GT, Hippenmeyer S. 2024.Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers. In: Neuronal Morphogenesis. Methods in Molecular Biology, vol. 2831, 283–299.","mla":"Miranda, Osvaldo, et al. “Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers.” <i>Neuronal Morphogenesis</i>, edited by Kazuhito Toyooka, 1st ed., vol. 2831, Springer Nature, 2024, pp. 283–99, doi:<a href=\"https://doi.org/10.1007/978-1-0716-3969-6_19\">10.1007/978-1-0716-3969-6_19</a>.","short":"O. Miranda, G.T. Cheung, S. Hippenmeyer, in:, K. Toyooka (Ed.), Neuronal Morphogenesis, 1st ed., Springer Nature, New York, NY, 2024, pp. 283–299.","ieee":"O. Miranda, G. T. Cheung, and S. Hippenmeyer, “Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers,” in <i>Neuronal Morphogenesis</i>, 1st ed., vol. 2831, K. Toyooka, Ed. New York, NY: Springer Nature, 2024, pp. 283–299."},"publisher":"Springer Nature","acknowledged_ssus":[{"_id":"Bio"}]},{"_id":"12542","article_processing_charge":"No","oa_version":"Published Version","day":"01","intvolume":"       111","department":[{"_id":"SiHi"}],"scopus_import":"1","article_type":"letter_note","publisher":"Elsevier","citation":{"ista":"Villalba Requena A, Hippenmeyer S. 2023. Going back in time with TEMPO. Neuron. 111(3), 291–293.","ieee":"A. Villalba Requena and S. Hippenmeyer, “Going back in time with TEMPO,” <i>Neuron</i>, vol. 111, no. 3. Elsevier, pp. 291–293, 2023.","mla":"Villalba Requena, Ana, and Simon Hippenmeyer. “Going Back in Time with TEMPO.” <i>Neuron</i>, vol. 111, no. 3, Elsevier, 2023, pp. 291–93, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.01.006\">10.1016/j.neuron.2023.01.006</a>.","short":"A. Villalba Requena, S. Hippenmeyer, Neuron 111 (2023) 291–293.","ama":"Villalba Requena A, Hippenmeyer S. Going back in time with TEMPO. <i>Neuron</i>. 2023;111(3):291-293. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.01.006\">10.1016/j.neuron.2023.01.006</a>","apa":"Villalba Requena, A., &#38; Hippenmeyer, S. (2023). Going back in time with TEMPO. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.01.006\">https://doi.org/10.1016/j.neuron.2023.01.006</a>","chicago":"Villalba Requena, Ana, and Simon Hippenmeyer. “Going Back in Time with TEMPO.” <i>Neuron</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.neuron.2023.01.006\">https://doi.org/10.1016/j.neuron.2023.01.006</a>."},"quality_controlled":"1","corr_author":"1","OA_type":"free access","date_published":"2023-02-01T00:00:00Z","publication":"Neuron","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"publication_status":"published","abstract":[{"lang":"eng","text":"In this issue of Neuron, Espinosa-Medina et al.1 present the TEMPO (Temporal Encoding and Manipulation in a Predefined Order) system, which enables the marking and genetic manipulation of sequentially generated cell lineages in vertebrate species in vivo."}],"date_updated":"2025-06-25T06:24:25Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.neuron.2023.01.006"}],"external_id":{"isi":["000994473300001"],"pmid":["36731425"]},"date_created":"2023-02-12T23:00:58Z","title":"Going back in time with TEMPO","author":[{"last_name":"Villalba Requena","first_name":"Ana","orcid":"0000-0002-5615-5277","full_name":"Villalba Requena, Ana","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061"}],"type":"journal_article","status":"public","publication_identifier":{"eissn":["1097-4199"]},"volume":111,"OA_place":"publisher","doi":"10.1016/j.neuron.2023.01.006","issue":"3","page":"291-293","language":[{"iso":"eng"}],"year":"2023","oa":1,"isi":1,"month":"02"},{"issue":"3","doi":"10.1152/jn.00172.2022","page":"501-512","language":[{"iso":"eng"}],"year":"2023","isi":1,"month":"03","type":"journal_article","acknowledgement":"The authors gratefully thank Dr. Silvia Arber, University of Basel and Friedrich Miescher Institute for Biomedical Research, for support and in whose lab the data were collected. For advice on statistical analysis, we thank Michael Bottomley from the Statistical Consulting Center, College of Science and Mathematics, Wright State University.","status":"public","publication_identifier":{"eissn":["1522-1598"],"issn":["0022-3077"]},"keyword":["Physiology","General Neuroscience"],"volume":129,"date_published":"2023-03-01T00:00:00Z","publication":"Journal of Neurophysiology","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","pmid":1,"publication_status":"published","abstract":[{"text":"Presynaptic inputs determine the pattern of activation of postsynaptic neurons in a neural circuit. Molecular and genetic pathways that regulate the selective formation of subsets of presynaptic inputs are largely unknown, despite significant understanding of the general process of synaptogenesis. In this study, we have begun to identify such factors using the spinal monosynaptic stretch reflex circuit as a model system. In this neuronal circuit, Ia proprioceptive afferents establish monosynaptic connections with spinal motor neurons that project to the same muscle (termed homonymous connections) or muscles with related or synergistic function. However, monosynaptic connections are not formed with motor neurons innervating muscles with antagonistic functions. The ETS transcription factor ER81 (also known as ETV1) is expressed by all proprioceptive afferents, but only a small set of motor neuron pools in the lumbar spinal cord of the mouse. Here we use conditional mouse genetic techniques to eliminate Er81 expression selectively from motor neurons. We find that ablation of Er81 in motor neurons reduces synaptic inputs from proprioceptive afferents conveying information from homonymous and synergistic muscles, with no change observed in the connectivity pattern from antagonistic proprioceptive afferents. In summary, these findings suggest a role for ER81 in defined motor neuron pools to control the assembly of specific presynaptic inputs and thereby influence the profile of activation of these motor neurons.","lang":"eng"}],"date_updated":"2024-10-21T06:01:28Z","external_id":{"pmid":["36695533"],"isi":["000957721600001"]},"date_created":"2023-02-15T14:46:14Z","title":"Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons","author":[{"full_name":"Ladle, David R.","first_name":"David R.","last_name":"Ladle"},{"last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"_id":"12562","article_processing_charge":"No","oa_version":"None","day":"01","intvolume":"       129","department":[{"_id":"SiHi"}],"scopus_import":"1","article_type":"original","publisher":"American Physiological Society","quality_controlled":"1","citation":{"chicago":"Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” <i>Journal of Neurophysiology</i>. American Physiological Society, 2023. <a href=\"https://doi.org/10.1152/jn.00172.2022\">https://doi.org/10.1152/jn.00172.2022</a>.","apa":"Ladle, D. R., &#38; Hippenmeyer, S. (2023). Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. <i>Journal of Neurophysiology</i>. American Physiological Society. <a href=\"https://doi.org/10.1152/jn.00172.2022\">https://doi.org/10.1152/jn.00172.2022</a>","ama":"Ladle DR, Hippenmeyer S. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. <i>Journal of Neurophysiology</i>. 2023;129(3):501-512. doi:<a href=\"https://doi.org/10.1152/jn.00172.2022\">10.1152/jn.00172.2022</a>","mla":"Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” <i>Journal of Neurophysiology</i>, vol. 129, no. 3, American Physiological Society, 2023, pp. 501–12, doi:<a href=\"https://doi.org/10.1152/jn.00172.2022\">10.1152/jn.00172.2022</a>.","short":"D.R. Ladle, S. Hippenmeyer, Journal of Neurophysiology 129 (2023) 501–512.","ieee":"D. R. Ladle and S. Hippenmeyer, “Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons,” <i>Journal of Neurophysiology</i>, vol. 129, no. 3. American Physiological Society, pp. 501–512, 2023.","ista":"Ladle DR, Hippenmeyer S. 2023. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology. 129(3), 501–512."}}]