IN SEARCH OF ADULT NEURAL STEM CELLS ORIGIN

During embryonic and postnatal development of the dentate gyrus (DG), neural stem cells (NSCs) proliferate, migrate and generate mature granule neurons. Unlike other brain regions, NSCs remain in the adult DG, mostly in a state of deep quiescence, with the ability to re-enter cell cycle and generate new neurons throughout life. The transitions back and forward from a proliferative state to a shallow quiescence or primed state ensure the maintenance of stem cell population. However, it is unclear when and how adult NSCs acquire quiescence substates during development.
We have determined that transcription factor Sox5 is required for the transition from quiescence to activation in adult NSCs and for the generation of new neurons (Li, et al., 2022). More recently (Medina-Menéndez et al, 2025), we have established that 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 quiescent state. Loss of Sox5 leads to an excess of NSCs in shallow quiescence, which are 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, a pathway required to maintain the correct levels of NSC quiescence. In conclusion, Sox5 is required to control the correct balance between shallow and deep quiescence, essential for establishing long-lasting adult neurogenesis. We will discuss new avenues to explore where and how the adult NSCs emerge during postnatal DG development.