Id4 Downstream of Notch2 Maintains Neural Stem Cell Quiescence in the Adult Hippocampus

Cell Reports
Runrui ZhangVerdon Taylor

Abstract

Neural stem cells (NSCs) in the adult mouse hippocampal dentate gyrus (DG) are mostly quiescent, and only a few are in cell cycle at any point in time. DG NSCs become increasingly dormant with age and enter mitosis less frequently, which impinges on neurogenesis. How NSC inactivity is maintained is largely unknown. Here, we found that Id4 is a downstream target of Notch2 signaling and maintains DG NSC quiescence by blocking cell-cycle entry. Id4 expression is sufficient to promote DG NSC quiescence and Id4 knockdown rescues Notch2-induced inhibition of NSC proliferation. Id4 deletion activates NSC proliferation in the DG without evoking neuron generation, and overexpression increases NSC maintenance while promoting astrogliogenesis at the expense of neurogenesis. Together, our findings indicate that Id4 is a major effector of Notch2 signaling in NSCs and a Notch2-Id4 axis promotes NSC quiescence in the adult DG, uncoupling NSC activation from neuronal differentiation.

Citations

Sep 10, 2020·The FEBS Journal·Taeko Kobayashi, Ryoichiro Kageyama
Jul 23, 2020·Frontiers in Cell and Developmental Biology·Miriam LabuschLaure Bally-Cuif
Oct 13, 2020·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Ryoichiro KageyamaHiromi Shimojo
Oct 21, 2020·Cells·Elena ParmigianiClaudio Giachino
Dec 10, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Nicolas DrayLaure Bally-Cuif
Dec 15, 2020·World Journal of Stem Cells·Meng LuoJiao-Jiao Zhou
Jul 30, 2020·Cell Stem Cell·Paloma Navarro NegredoAnne Brunet
Jul 25, 2021·Cell and Tissue Research·Yu-Hsuan ChuChristian Schachtrup
Sep 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Hiroyoshi DoiKinichi Nakashima
Nov 28, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Shogo SatoRicardo Orozco-Solis

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