FIP200 is required for maintenance and differentiation of postnatal neural stem cells

Despite recent studies showing depletion of hematopoietic stem cells (HSCs) pool accompanied by increased intracellular ROS upon autophagy inhibition, it remains unknown whether autophagy is essential in the maintenance of other stem cells. Moreover, it is unclear whether and how the aberrant ROS increase causes depletion of stem cells. Here, we report that ablation of FIP200, an essential gene for autophagy induction in mammalian cells, results in a progressive loss of neural stem cells (NSCs) pool and impairment in neuronal differentiation specifically in the postnatal brain, but not the embryonic brain, in mice. The defect in maintaining the postnatal NSC pool was caused by p53-dependent apoptotic responses and cell cycle arrest. However, the impaired neuronal differentiation was rescued by anti-oxidant NAC treatment, but not by p53 inactivation. These data reveal a role of FIP200-mediated autophagy in the maintenance and functions of NSCs through regulation of oxidative state.