Essential Roles of Notch Signaling in Maintenance of Neural Stem Cells in Developing and Adult Brains
By Itaru Imayoshi, Masayuki Sakamoto, Masahiro Yamaguchi, K. Mori, Ryoichiro Kageyama. 2010
689 citations recorded by the source corpus.
Activation of Notch signaling induces the expression of transcriptional repressor genes such as Hes1, leading to repression of proneural gene expression and maintenance of neural stem/progenitor cells. However, a requirement for Notch signaling in the telencephalon was not clear, because in Hes1;Hes3;Hes5 triple-mutant mice, neural stem/progenitor cells are depleted in most regions of the developing CNS, but not in the telencephalon. Here, we investigated a role for Notch signaling in the telencephalon by generating tamoxifen-inducible conditional knock-out mice that lack Rbpj, an intracellular signal mediator of all Notch receptors. When Rbpj was deleted in the embryonic brain, almost all telencephalic neural stem/progenitor cells prematurely differentiated into neurons and were depleted. When Rbpj was deleted in the adult brain, all neural stem cells differentiated into transit-amplifying cells and neurons. As a result, neurogenesis increased transiently, but 3 months later all neural stem cells were depleted and neurogenesis was totally lost. These results indicated an absolute requirement of Notch signaling for the maintenance of neural stem cells and a proper control of neurogenesis in both embryonic and adult brains.
Subfields: Cancer Research, Developmental Neuroscience, Molecular Biology
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Citations in the corpus
- Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “In the adult SVZ, nestin-CreER-mediated deletion of RBPj, a downstream mediator of all Notch receptors, activates radial glia-like cells to differentiate into transient amplifying cells, resulting in depletion of quiescent neural precursors and loss of continuous neurogenesis (Imayoshi et al., 2010)”
- RBPJκ-Dependent Signaling Is Essential for Long-Term Maintenance of Neural Stem Cells in the Adult Hippocampus (2010, background): “1) and the adult subventricular zone (Imayoshi et al., 2010) show robust activity of the Hes5 promoter.”
- Development and Evolution of the Human Neocortex (2011, neutral): “, 2004), either singly or in combination, as well as of the NICD signaling mediator CBF1 (RBPJ) (Mizutani et al., 2007; Imayoshi et al., 2010).”
- Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury. (2015, neutral): “6 Cell Stem Cell 17, 1–12, September 3, 2015 ª2015 Elsevier Inc. Notch signaling has been proposed as an essential regulator of quiescence and as a generator of heterogeneity in NSCs (Basak et al., 2012; Giachino and Taylor, 2014; Imayoshi et al., 2010; Kawaguchi et al., 2013).”