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Regional differences in progenitor metabolism shape brain growth during development

Mammals have particularly large forebrains compared with other brain parts, yet the developmental mechanisms underlying this regional expansion remain poorly understood. Here, we provide a single-cell-resolution birthdate atlas of the mouse brain (www.neurobirth.org), which reveals that while hindbr...

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Main Authors: Baumann, Natalia (Author) , Wagener, Jan Robin (Author) , Javed, Awais (Author) , Conti, Eleonora (Author) , Abe, Philipp (Author) , Lopes, Andrea (Author) , Sansevrino, Roberto (Author) , Lavalley, Adrien (Author) , Magrinelli, Elia (Author) , Szalai, Timea (Author) , Fuciec, Daniel (Author) , Ferreira, Clothilde (Author) , Fièvre, Sabine (Author) , Fouassier, Andreane (Author) , D’Amico, Davide (Author) , Harschnitz, Oliver (Author) , Jabaudon, Denis (Author)
Format: Article (Journal)
Language:English
Published: June 26, 2025
In: Cell
Year: 2025, Volume: 188, Issue: 13, Pages: 3567-3582.e20
ISSN:1097-4172
DOI:10.1016/j.cell.2025.04.003
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.cell.2025.04.003
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867425004052
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Author Notes:Natalia Baumann, Robin J. Wagener, Awais Javed, Eleonora Conti, Philipp Abe, Andrea Lopes, Roberto Sansevrino, Adrien Lavalley, Elia Magrinelli, Timea Szalai, Daniel Fuciec, Clothilde Ferreira, Sabine Fièvre, Andreane Fouassier, Davide D’Amico, Oliver Harschnitz, and Denis Jabaudon
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Summary:Mammals have particularly large forebrains compared with other brain parts, yet the developmental mechanisms underlying this regional expansion remain poorly understood. Here, we provide a single-cell-resolution birthdate atlas of the mouse brain (www.neurobirth.org), which reveals that while hindbrain neurogenesis is transient and restricted to early development, forebrain neurogenesis is temporally sustained through reduced consumptive divisions of ventricular zone progenitors. This atlas additionally reveals region-specific patterns of direct and indirect neurogenesis. Using single-cell RNA sequencing, we identify evolutionarily conserved cell-cycle programs and metabolism-related molecular pathways that control regional temporal windows of proliferation. We identify the late neocortex-enriched mitochondrial protein FAM210B as a key regulator using in vivo gain- and loss-of-function experiments. FAM210B elongates mitochondria and increases lactate production, which promotes progenitor self-replicative divisions and, ultimately, the larger clonal size of their progeny. Together, these findings indicate that spatiotemporal heterogeneity in mitochondrial function regulates regional progenitor cycling behavior and associated clonal neuronal production during brain development.
Item Description:Gesehen am 20.01.2026
Physical Description:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2025.04.003

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