Sox5 controls the establishment of quiescence in neural stem cells during postnatal development

Abstract

Adult stem cells niches relays in the acquisition of a reversible state of quiescence to ensure long-lasting DNA integrity and cell expansion. Neural stem cells (NSCs) in the dentate gyrus (DG) enter quiescence before the adult hippocampal neurogenic niche is fully established. However, the mechanisms controlling NSC first quiescence entry and quiescence deepness are largely unknown. Using conditional mutant mouse during embryonic or postnatal stages, we have determined that transcription factor Sox5 is required to restrict first entry in quiescence. Moreover, we have found a critical window during the second postnatal week when NSCs build up a shallow or primed quiescent state. Loss of Sox5 leads to an excess of primed NSCs prone to activate leading to a neurogenic burst in the adult DG and precocious depletion of the NSC pool. Mechanistically, Sox5 prevent an excess of BMP canonical signaling activation, a pathway that we have now determined is associated to NSC primed state. In conclusion, our results demonstrate that Sox5 is required to control the correct balance between primed and deep quiescence during the first postnatal weeks of DG development, a balance which is essential for establishing long-lasting adult neurogenesis.