---
OA_place: repository
OA_type: green
_id: '19717'
abstract:
- lang: eng
  text: Radial glial progenitors (RGPs) generate all projection neurons (PNs) in the
    cerebral cortex through incompletely understood processes. Herein, we combine
    Mosaic Analysis with Double Markers (MADM)-based clonal analysis at embryonic
    days 12.5 and 13.5 with early postnatal callosal tracing to reveal a lineage progression
    that challenges the inside-outside model of cortical development and the conventional
    view of an invariable sequence of asymmetric neurogenic divisions. Our data demonstrate
    that early multipotent RGPs generate all extra-telencephalic (ET) and intra-telencephalic
    (IT) PNs across all layers through parallel sublineages and the random specification,
    during the earliest neurogenic divisions, of fate-restricted daughter RGPs. While
    the neuronal production of the parental multipotent RGPs consists of small ET-PN
    or IT-PN outputs, fate-restricted RGPs produce larger translaminar outputs spanning
    deep and upper layers of only IT-PNs, the predominant mammalian PN subtype. We
    further show that the emergence of IT-PN fate-restricted RGPs also leads to quantitatively
    and temporally stereotyped neurogenesis population-wise.
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"
article_processing_charge: No
author:
- first_name: I
  full_name: Varela-Martínez, I
  last_name: Varela-Martínez
- first_name: Ana
  full_name: Villalba Requena, Ana
  id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
  last_name: Villalba Requena
  orcid: 0000-0002-5615-5277
- first_name: J.
  full_name: Garcia-Marqués, J.
  last_name: Garcia-Marqués
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
- first_name: M.
  full_name: Nieto, M.
  last_name: Nieto
citation:
  ama: Varela-Martínez I, Villalba Requena A, Garcia-Marqués J, Hippenmeyer S, Nieto
    M. Early emergence of projection-subtype fate-restricted radial glial progenitors
    orchestrates neocortical neurogenesis. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2025.05.07.652665">10.1101/2025.05.07.652665</a>
  apa: Varela-Martínez, I., Villalba Requena, A., Garcia-Marqués, J., Hippenmeyer,
    S., &#38; Nieto, M. (n.d.). Early emergence of projection-subtype fate-restricted
    radial glial progenitors orchestrates neocortical neurogenesis. <i>bioRxiv</i>.
    <a href="https://doi.org/10.1101/2025.05.07.652665">https://doi.org/10.1101/2025.05.07.652665</a>
  chicago: Varela-Martínez, I, Ana Villalba Requena, J. Garcia-Marqués, Simon Hippenmeyer,
    and M. Nieto. “Early Emergence of Projection-Subtype Fate-Restricted Radial Glial
    Progenitors Orchestrates Neocortical Neurogenesis.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2025.05.07.652665">https://doi.org/10.1101/2025.05.07.652665</a>.
  ieee: I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer,
    and M. Nieto, “Early emergence of projection-subtype fate-restricted radial glial
    progenitors orchestrates neocortical neurogenesis,” <i>bioRxiv</i>. .
  ista: Varela-Martínez I, Villalba Requena A, Garcia-Marqués J, Hippenmeyer S, Nieto
    M. Early emergence of projection-subtype fate-restricted radial glial progenitors
    orchestrates neocortical neurogenesis. bioRxiv, <a href="https://doi.org/10.1101/2025.05.07.652665">10.1101/2025.05.07.652665</a>.
  mla: Varela-Martínez, I., et al. “Early Emergence of Projection-Subtype Fate-Restricted
    Radial Glial Progenitors Orchestrates Neocortical Neurogenesis.” <i>BioRxiv</i>,
    doi:<a href="https://doi.org/10.1101/2025.05.07.652665">10.1101/2025.05.07.652665</a>.
  short: I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer,
    M. Nieto, BioRxiv (n.d.).
date_created: 2025-05-20T10:19:29Z
date_published: 2025-05-07T00:00:00Z
date_updated: 2026-08-13T07:16:48Z
day: '07'
department:
- _id: SiHi
doi: 10.1101/2025.05.07.652665
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2025.05.07.652665
month: '05'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
status: public
title: Early emergence of projection-subtype fate-restricted radial glial progenitors
  orchestrates neocortical neurogenesis
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...