Regional Differences In Progenitor Metabolism Shape Brain Growth During Development Natalia Baumann by Natalia Baumann, Robin J. Wagener, Awais Javed, ..., Davide D’amico, Oliver Harschnitz, Denis Jabaudon 101016/JCELL202504003 instant download after payment.

SUMMARYMammals 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 neurogenesisis transient and restricted to early development, forebrain neurogenesis is temporally sustained throughreduced consumptive divisions of ventricular zone progenitors. This atlas additionally reveals region-specificpatterns of direct and indirect neurogenesis. Using single-cell RNA sequencing, we identify evolutionarilyconserved cell-cycle programs and metabolism-related molecular pathways that control regional temporalwindows of proliferation. We identify the late neocortex-enriched mitochondrial protein FAM210B as a keyregulator 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 largerclonal 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.