Essential Roles of Notch Signaling in Maintenance of Neural Stem Cells in Developing and Adult Brains
TLDR
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 is indicated.Abstract:
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.read more
Citations
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Adult neurogenesis in the mammalian brain: significant answers and significant questions.
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Development and Evolution of the Human Neocortex
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Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.
Enric Llorens-Bobadilla,Sheng Zhao,Avni Baser,Gonzalo Saiz-Castro,Klara Zwadlo,Ana Martin-Villalba +5 more
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Notch Signaling in Development, Tissue Homeostasis, and Disease
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The Varied Roles of Notch in Cancer
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