FIP200 is required for maintenance and differentiation of postnatal neural stem cells
Open Access
- 31 March 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 16 (5), 532-542
- https://doi.org/10.1038/nn.3365
Abstract
Wang et al. find that deletion of FIP200, a protein essential for autophagy, leads to deficits in the maintenance and differentiation of postnatal neural stem cells (NSC). These effects are rescued by an antioxidant treatment, suggesting that FIP200-mediated autophagy regulates neurogenesis by controlling the oxidative state of NSC. Despite recent studies showing that inhibition of autophagy depletes the hematopoietic stem cell pool and increases intracellular reactive oxygen species (ROS), 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 (also known as Rb1cc1), a gene essential for autophagy induction in mammalian cells, results in a progressive loss of neural stem cells (NSCs) 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 treatment with the antioxidant N-acetylcysteine but not by p53 inactivation. These data reveal that FIP200-mediated autophagy contributes to the maintenance and functions of NSCs through regulation of oxidative state.Keywords
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