ENAGenomicsCaolab, Developmental Neurobiology, St. Jude Children's Research Hospitalhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1201061Mus musculusThe embryonic ventral telencephalon (subpallium) gives rise to extremely diverse types of cells. Although it is known that subpallial neural progenitors possess characteristics distinct from their cortical counterparts, the mechanisms governing their lineage progression are poorly understood. Here we show that TEAD, the key DNA-binding factor of the Hippo pathway, promotes lineage progression of subpallial neural progenitors the loss of TEAD1 and TEAD2 (TEAD1/2) during mammalian brain development expands early progenitors and reduces late progenitors uniquely in the subpallium, but not in the cortex. Importantly, this function of TEAD1/2 is independent of their canonical partners in the Hippo pathway, transcriptional coactivators YAP and TAZ (YAP/TAZ), as the loss of YAP/TAZ leads to the opposite phenotype—a depletion of early progenitors and increase in late progenitors. We further show that TEAD1/2 act at least in part by inhibiting Notch signaling and by cooperating with INSM1. It has been shown that orthologs of TEAD and INSM1 cooperate to regulate neuronal cell fate decisions in worms and flies. Our study reveals a remarkable evolutionary conservation of the function of this transcription factor complex during metazoan neural development. Overall design: The MGEs from wild-type mice at E12.5 and E15.5, as well as Tead1/2 and Yap/Taz knockout mutant mice and appropriate controls at E14.5, were collected for scRNASeq analysisxref:PubMed:40389325ENAfalseTEAD promotes lineage progression of subpallial neural progenitor cells independent of YAP/TAZTEAD promotes lineage progression of subpallial neural progenitor cells independent of YAP/TAZ2025-09-242025-07-17PRJNA1201061GSE2850251009040389325