2010年3月
Essential Roles of Notch Signaling in Maintenance of Neural Stem Cells in Developing and Adult Brains
JOURNAL OF NEUROSCIENCE
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- 巻
- 30
- 号
- 9
- 開始ページ
- 3489
- 終了ページ
- 3498
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1523/JNEUROSCI.4987-09.2010
- 出版者・発行元
- SOC NEUROSCIENCE
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.
- リンク情報
- ID情報
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- DOI : 10.1523/JNEUROSCI.4987-09.2010
- ISSN : 0270-6474
- PubMed ID : 20203209
- Web of Science ID : WOS:000275191000035