期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 51, 页码 20558-20563出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0710156104
关键词
adult neurogenesis; Mash1; proneural; stem cell
资金
- NIA NIH HHS [R01 AG019394, AG019394] Funding Source: Medline
- NICHD NIH HHS [R01 HD045481, HD045481] Funding Source: Medline
- NIMH NIH HHS [R01 MH067715] Funding Source: Medline
- NINDS NIH HHS [R01 NS047200, NS047200] Funding Source: Medline
The lifelong addition of neurons to the hippocampus is a remarkable form of structural plasticity, yet the molecular controls over proliferation, neuronal fate determination, survival, and maturation are poorly understood. Expression of Notch1 was found to change dynamically depending on the differentiation state of neural precursor cells. Through the use of inducible gain- and loss-of-function of Notch1 mice we show that this membrane receptor is essential to these distinct processes. We found in vivo that activated Notch1 overexpression induces proliferation, whereas gamma-secretase inhibition or genetic ablation of Notch1 promotes cell cycle exit, indicating that the level of activated Notch1 regulates the magnitude of neurogenesis from postnatal progenitor cells. Abrogation of Notch signaling in vivo or in vitro leads to a transition from neural stem or precursor cells to transit-amplifying cells or neurons. Further, genetic Notch1 manipulation modulates survival and dendritic morphology of newborn granule cells. These results provide evidence for the expansive prevalence of Notch signaling in hippocampal morphogenesis and plasticity, suggesting that Notch1 could be a target of diverse traumatic and environmental modulators of adult neurogenesis.
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