RRC ID 69000
Author Harada Y, Yamada M, Imayoshi I, Kageyama R, Suzuki Y, Kuniya T, Furutachi S, Kawaguchi D, Gotoh Y.
Title Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module.
Journal Nat Commun
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.
Volume 12(1)
Pages 6562
Published 2021-11-12
DOI 10.1038/s41467-021-26605-0
PII 10.1038/s41467-021-26605-0
PMID 34772946
PMC PMC8589987
MeSH Adult Stem Cells / metabolism* Animals Basic Helix-Loop-Helix Transcription Factors / metabolism Brain / cytology Cell Cycle / genetics Cell Cycle / physiology Cell Cycle Checkpoints / genetics Cell Cycle Checkpoints / physiology* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Embryonic Stem Cells Gene Expression Lateral Ventricles / metabolism Mice Nervous System Neurogenesis / genetics Neurogenesis / physiology* Receptor, Notch1 Repressor Proteins / metabolism
IF 12.121
Mice RBRC01151 RBRC02707