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Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module

ABSTRACT: Quiescent neural stem cells (NSCs) in the adult mouse brain are the source of neurogenesis that regulates innate and adaptive behaviors. Adult NSCs in the subventricular zone are derived from a subpopulation of embryonic neural stem-progenitor cells (NPCs) that is characterized by a slower cell cycle relative to the more abundant rapid cycling NPCs that build the brain. Yet, how slow cell cycle can cause the establishment of adult NSCs remains largely unknown. Here, we demonstrate that Notch and an effector Hey1 form a module that is upregulated by cell cycle arrest in slowly dividing NPCs. In contrast to the oscillatory expression of the Notch effectors Hes1 and Hes5 in fast cycling progenitors, Hey1 displays a non-oscillatory stationary expression pattern and contributes to the long-term maintenance of NSCs. These findings reveal a novel division of labor in Notch effectors where cell cycle rate biases effector selection and cell fate. Adult neural stem cells are derived from an embryonic population of slowcycling progenitor cells, though how reduced cycling speed leads to establishment of the adult population has remained elusive. Here they show that non-oscillatory Notch-Hey signaling induced by slow-cycling contributes to long term maintenance of neural stem cells.

SUBMITTER: Harada Y

PROVIDER: S-EPMC8589987 | biostudies-literature |

REPOSITORIES: biostudies-literature

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