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

First Author  Zhang R Year  2019
Journal  Cell Rep Volume  28
Issue  6 Pages  1485-1498.e6
PubMed ID  31390563 Mgi Jnum  J:294955
Mgi Id  MGI:6458203 Doi  10.1016/j.celrep.2019.07.014
Citation  Zhang R, et al. (2019) Id4 Downstream of Notch2 Maintains Neural Stem Cell Quiescence in the Adult Hippocampus. Cell Rep 28(6):1485-1498.e6
abstractText  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.
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