{"month":"05","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.05.07.652665"}],"date_published":"2025-05-07T00:00:00Z","oa":1,"title":"Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis","oa_version":"Preprint","publication_status":"published","publication":"bioRxiv","_id":"19717","date_updated":"2025-05-28T06:37:46Z","article_processing_charge":"No","department":[{"_id":"SiHi"}],"OA_type":"green","doi":"10.1101/2025.05.07.652665","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","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>.","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.","short":"I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer, M. Nieto, BioRxiv (2025).","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>.","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>","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>.","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>"},"day":"07","language":[{"iso":"eng"}],"date_created":"2025-05-20T10:19:29Z","OA_place":"repository","type":"preprint","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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"}],"author":[{"full_name":"Varela-Martínez, I","first_name":"I","last_name":"Varela-Martínez"},{"orcid":"0000-0002-5615-5277","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","first_name":"Ana","last_name":"Villalba Requena","full_name":"Villalba Requena, Ana"},{"last_name":"Garcia-Marqués","first_name":"J.","full_name":"Garcia-Marqués, J."},{"first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"},{"full_name":"Nieto, M.","last_name":"Nieto","first_name":"M."}],"status":"public","year":"2025"}