期刊
DEVELOPMENTAL NEUROSCIENCE
卷 28, 期 1-2, 页码 49-57出版社
KARGER
DOI: 10.1159/000090752
关键词
Notch activity; developing central nervous system; cell death
资金
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH068469] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS036437] Funding Source: NIH RePORTER
- NIMH NIH HHS [5 R01 MH068469-02] Funding Source: Medline
- NINDS NIH HHS [NS 07457-03, NS036437] Funding Source: Medline
Many cells in the mammalian brain undergo apoptosis as a normal and critical part of development but the signals that regulate the survival and death of neural progenitor cells and the neurons they produce are not well understood. The Notch signaling pathway is involved in multiple decision points during development and has been proposed to regulate the survival and apoptosis of neural progenitor cells in the developing brain; however, previous experiments have not resolved whether Notch activity is pro- or anti-apoptotic. To elucidate the function of Notch signaling in the survival and death of cells in the nervous system, we have produced single and compound Notch conditional mutants in which Notch1 and Notch3 are removed at different times during brain development and in different populations of cells. We show here that a large number of neural progenitor cells, as well as differentiating neurons, undergo apoptosis in the absence of Notch1 and Notch3, suggesting that Notch activity promotes the survival of both progenitors and newly differentiating cells in the developing nervous system. Finally, we show that postmitotic neurons do not require Notch activity indefinitely to regulate their survival since elevated levels of cell death are observed only during embryogenesis in the Notch mutants and are not detected in neonates.
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