Journal
STEM CELLS
Volume 28, Issue 12, Pages 2162-2171Publisher
WILEY-BLACKWELL
DOI: 10.1002/stem.541
Keywords
Nestin; Intermediate filament; Apoptosis; Neural stem cells
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Funding
- Human Frontier Science Program
- National Natural Science Foundation of China [30671023]
- National Basic Research Program of China [2009CB522100, 2010CB945400]
- Key Scientific and Technological Projects of Guangdong Province [2007A032100003]
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The intermediate filament protein, nestin, is a widely employed marker of multipotent neural stem cells (NSCs). Recent in vitro studies have implicated nestin in a number of cellular processes, but there is no data yet on its in vivo function. Here, we report the construction and functional characterization of Nestin knockout mice. We found that these mice show embryonic lethality, with neuroepithelium of the developing neural tube exhibiting significantly fewer NSCs and much higher levels of apoptosis. Consistent with this in vivo observation, NSC cultures derived from knockout embryos show dramatically reduced self-renewal ability that is associated with elevated apoptosis but no overt defects in cell proliferation or differentiation. Unexpectedly, nestin deficiency has no detectable effect on the integrity of the cytoskeleton. Furthermore, the knockout of Vimentin, which abolishes nestin's ability to polymerize into intermediate filaments in NSCs, does not lead to any apoptotic phenotype. These data demonstrate that nestin is important for the proper survival and self-renewal of NSCs, and that this function is surprisingly uncoupled from nestin's structural involvement in the cytoskeleton. STEM CELLS 2010; 28: 2162-2171
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