PRDM16 establishes lineage-specific transcriptional program to promote temporal progression of neural progenitors in the mouse neocortex

Abstract

36Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, 37 accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that 38 drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here we 39 reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early 40 to late phases of neurogenesis in the mouse neocortex. Prdm16 mutant RG delays the timely 41 progression of RG, leading to defective cortical laminar organization. We show that PRDM16 42 regulates expression of neuronal specification genes and a subset of genes that are dynamically 43 expressed between mid-and late-neurogenesis. Our genomic analysis suggests that PRDM16 44 suppresses target gene expression through maintaining chromatin accessibility of permissive 45 enhancers. Altogether, our results demonstrate a critical role of PRDM16 in establishing stage-46 specific gene expression program of RG during cortical neurogenesis. These findings also 47 support a model where progenitor cells are primed with daughter cell gene expression program 48 for rapid cell differentiation.