biostudies-literatureBarao SNIMH NIH HHSNHGRI NIH HHSNINDS NIH HHS8043https://www.ebi.ac.uk/biostudies/studies/S-EPMC11399407biostudies-literatureUnknown15(1)The neocortex varies in size and complexity among mammals due to the tremendous variability in the number and diversity of neuronal subtypes across species. The increased cellular diversity is paralleled by the expansion of the pool of neocortical progenitors and the emergence of indirect neurogenesis during brain evolution. The molecular pathways that control these biological processes and are disrupted in neurological disorders remain largely unknown. Here we show that the transcription factors BRN1 and BRN2 have an evolutionary conserved function in neocortical progenitors to control their proliferative capacity and the switch from direct to indirect neurogenesis. Functional studies in mice and ferrets show that BRN1/2 act in concert with NOTCH and primary microcephaly genes to regulateNature communicationsConserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion.PMC11399407RF1 MH121539K99 NS112604R01 HG012357R00 NS112604Vistein RGoff LBarao SLlongueras JPBae BIWalsh CASmith RSStein-O'Brien GMuller UNielsen KJXu YfalseConserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion.The neocortex varies in size and complexity among mammals due to the tremendous variability in the number and diversity of neuronal subtypes across species. The increased cellular diversity is paralleled by the expansion of the pool of neocortical progenitors and the emergence of indirect neurogenesis during brain evolution. The molecular pathways that control these biological processes and are disrupted in neurological disorders remain largely unknown. Here we show that the transcription factors BRN1 and BRN2 have an evolutionary conserved function in neocortical progenitors to control their proliferative capacity and the switch from direct to indirect neurogenesis. Functional studies in mice and ferrets show that BRN1/2 act in concert with NOTCH and primary microcephaly genes to regulate2024-01-01T00:00:00Z2024 Sep2026-06-02T04:52:16.356Z2025-04-04T11:36:38.254ZS-EPMC113994073927167510.1038/s41467-024-52443-x