Prdm16 regulates the postnatal fate of embryonic radial glia via Vcam1-dependent mechanisms.

Abstract

The mammalian brain undergoes rapid and extensive neurogenesis during the embryonic stage and limited neurogenesis during the adult stage, which results in ineffective repair of neural circuits in adults. Currently, the molecular mechanisms regulating the postnatal termination of neurogenesis and the disappearance of embryonic radial glia, the neural stem cells (NSCs) responsible for neurogenesis, are largely unknown. Here, we show that genetic deletion of PR domain-containing 16 (Prdm16) from NSCs leads to the retention of radial glia in adulthood and prolonged postnatal neuroblast production. Mechanistically, Prdm16 induces a postnatal reduction in Vascular Cell Adhesion Molecule 1 (Vcam1). The extended presence of radial glia and neurogenesis phenotype is rescued in Prdm16-Vcam1 double knockout mice. These findings demonstrate that the inhibition of Vcam1 by Prdm16 promotes the postnatal cessation of neurogenesis and the disappearance of embryonic radial glia and provide valuable insights for regenerative medicine aimed at treating central nervous system disorders.