---
OA_place: repository
OA_type: green
_id: '19762'
abstract:
- lang: eng
text: The cerebral cortex must contain the appropriate numbers of neurons in each
layer to acquire its proper functional organization. Accordingly, neurogenesis
requires precise regulation along development. Cortical neurons are made either
directly by Radial Glia Cells (RGCs) that self- consume, or indirectly from RGCs
via Intermediate Progenitor Cells (IPCs) and largely preserving the RGC pool.
According to the standing model of cortical development, Direct Neurogenesis predominates
at early stages of development, and progressively shifts to Indirect Neurogenesis,
which predominates at late stages. However, neurogenesis at early stages should
be compatible with RGC amplification, and neurogenesis at late stages needs to
involve RGC consumption, which seems in conflict with the standing model. Here
we studied the modes of neurogenesis along cortical development using multiple
approaches, including birthdating, live imaging and MADM clone labeling. Contrary
to the established dogma, our data show that Indirect Neurogenesis clearly predominates
at early developmental stages, gradually shifting to Direct Neurogenesis at late
stages. These findings challenge the current model of cortical neurogenesis, and
prompt a re-evaluation of previous and ongoing work about the genetic and molecular
mechanisms regulating this process.
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)."
article_processing_charge: No
author:
- first_name: Adrián
full_name: Cárdenas, Adrián
last_name: Cárdenas
- first_name: Irem
full_name: Çelik, Irem
last_name: Çelik
- first_name: Alexandre
full_name: Espinós, Alexandre
last_name: Espinós
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Lara
full_name: López-González, Lara
last_name: López-González
- first_name: Lucia
full_name: del-Valle-Anton, Lucia
last_name: del-Valle-Anton
- first_name: Virginia
full_name: Fernández, Virginia
last_name: Fernández
- first_name: Salma
full_name: Amin, Salma
last_name: Amin
- first_name: Enrico
full_name: Negri, Enrico
last_name: Negri
- first_name: Eduardo Fernández
full_name: Ortuño, Eduardo Fernández
last_name: Ortuño
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Víctor
full_name: Borrell, Víctor
last_name: Borrell
biorxivid: 1
citation:
ama: Cárdenas A, Çelik I, Espinós A, et al. Early indirect neurogenesis transitions
to late direct neurogenesis in mouse cerebral cortex development. bioRxiv.
doi:10.1101/2025.05.22.655488
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. bioRxiv. https://doi.org/10.1101/2025.05.22.655488
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.” BioRxiv, n.d. https://doi.org/10.1101/2025.05.22.655488.
ieee: A. Cárdenas et al., “Early indirect neurogenesis transitions to late
direct neurogenesis in mouse cerebral cortex development,” bioRxiv. .
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, 10.1101/2025.05.22.655488.
mla: Cárdenas, Adrián, et al. “Early Indirect Neurogenesis Transitions to Late Direct
Neurogenesis in Mouse Cerebral Cortex Development.” BioRxiv, doi:10.1101/2025.05.22.655488.
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.).
date_created: 2025-05-29T10:45:55Z
date_published: 2025-05-23T00:00:00Z
date_updated: 2026-08-13T07:18:38Z
day: '23'
department:
- _id: SiHi
doi: 10.1101/2025.05.22.655488
external_id:
biorxivid:
- 10.1101/2025.05.22.655488
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2025.05.22.655488
month: '05'
oa: 1
oa_version: Preprint
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
publication: bioRxiv
publication_status: submitted
status: public
title: Early indirect neurogenesis transitions to late direct neurogenesis in mouse
cerebral cortex development
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...