Fig. 6: Role of proteostasis and autophagy in the acquisition of NSC dormancy during development.

a Schematic representation illustrating the proposed protein aggregate dynamics and regulation of the autophagy-lysosomal pathway in the switch between the active (A) and the quiescent (Q) NSC states, both in vitro in NSPC cultures and in vivo in acutely isolated NSCs/RGLs. b Schematic representation illustrating the in vivo role of Atg7-dependent autophagy in quiescence acquisition and in the transition of developmental NSCs into their adult form. Upper panel, developmental dentate gyrus (DG) NSCs arise perinatally from NSCs that migrate out of the embryonic dentate neuroepithelium (DNE). Throughout postnatal development, they acquire a radial glia-like (RGL) morphology and they continue to proliferate until they transition to an adult-like quiescent state. Lower panel, Atg7 is required early in dentate gyrus postnatal development for the acquisition of NSC/RGL quiescence. It is also required later on for the maintenance of RGL quiescence during the postnatal period, precluding the reactivation of the cells. The genetic strategy employed demonstrates that the autophagy gene Atg7 is cell-intrinsically required for the proper regulation of quiescence in RGLs when they are being spared as a dormant NSC reservoir. Representations shown in (a and b) were created with BioRender.com. A, Active NSPCs. Q, Quiescent NSPCs. Qrev, quiescence-reverted NSPCs. P3, Postnatal day 3. P21, Postnatal day 21. ALP, Autophagy–lysosomal Pathway. NSCs, Neural Stem Cells. DG, Dentate Gyrus. DNE, Dentate Neuroepithelium. BrdU, Bromodeoxyuridine.