Proneural genes define ground-state rules to regulate neurogenic patterning and cortical folding.

ABSTRACT: Asymmetric neuronal expansion is thought to drive evolutionary transitions between lissencephalic and gyrencephalic cerebral cortices. We report that Neurog2 and Ascl1 proneural genes together sustain neurogenic continuity and lissencephaly in rodent cortices. Using transgenic reporter mice and human cerebral organoids, we found that Neurog2 and Ascl1 expression defines a continuum of four lineage-biased neural progenitor cell (NPC) pools. Double⁺ NPCs, at the hierarchical apex, are least lineage restricted due to Neurog2-Ascl1 cross-repression and display unique features of multipotency (more open chromatin, complex gene regulatory network, G₂ pausing). Strikingly, selectively eliminating double⁺ NPCs by crossing Neurog2-Ascl1 split-Cre mice with diphtheri

SUBMITTER: Han S 

PROVIDER: S-EPMC12080610 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature