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

Yujin Harada, Mayumi Yamada, Itaru Imayoshi, Ryoichiro Kageyama, Yutaka Suzuki, Takaaki Kuniya, Shohei Furutachi, Daichi Kawaguchi () and Yukiko Gotoh ()
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Yujin Harada: The University of Tokyo
Mayumi Yamada: Institute for Frontier Life and Medical Sciences, Kyoto University
Itaru Imayoshi: Institute for Frontier Life and Medical Sciences, Kyoto University
Ryoichiro Kageyama: Institute for Frontier Life and Medical Sciences, Kyoto University
Yutaka Suzuki: The University of Tokyo
Takaaki Kuniya: The University of Tokyo
Shohei Furutachi: The University of Tokyo
Daichi Kawaguchi: The University of Tokyo
Yukiko Gotoh: The University of Tokyo

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26605-0

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