Dorsal-Ventral Differences in Neural Stem Cell Quiescence Are Induced by p57KIP2/Dacapo

Quiescent neural stem cells (NSCs) in the adult brain are regenerative cells that could be activated therapeutically to repair damage. It is becoming apparent that quiescent NSCs exhibit heterogeneity in their propensity for activation and in the progeny that they generate. We discovered recently that NSCs undergo quiescence in either G0 or G2 in the Drosophila brain, challenging the notion that all quiescent stem cells are G0 arrested. We found that G2-quiescent NSCs become activated prior to G0 NSCs. Here, we show that the cyclin-dependent kinase inhibitor Dacapo (Dap; ortholog of p57KIP2) determines whether NSCs enter G0 or G2 quiescence during embryogenesis. We demonstrate that the dorsal patterning factor, Muscle segment homeobox (Msh; ortholog of MSX1/2/3) binds directly to the Dap locus and induces Dap expression in dorsal NSCs, resulting in G0 arrest, while more ventral NSCs undergo G2 quiescence. Our results reveal region-specific regulation of stem cell quiescence. [Display omitted] •p57/Dap determines whether neural stem cells enter G0 quiescence or G2 quiescence•The dorsal patterning factor MSX/Msh promotes p57/Dap expression and G0 quiescence•Ventral stem cells instead express NKX/Vnd and undergo G2 quiescence•Stem cells undergo distinct types of quiescence depending on axial identity Otsuki and Brand reveal that axis patterning during embryogenesis primes neural stem cells (NSCs) to undergo different types of quiescence. Dorsal NSCs express the patterning factor MSX/Msh, which triggers p57KIP2/Dap expression and G0 quiescence. Ventral NSCs, negative for MSX/Msh, undergo G2 quiescence. G2 cells become activated before G0 cells post-embryonically.