Stem Cells  28:2162 (2010)

Nestin is Required for the Proper Self-Renewal of Neural Stem Cells.

DONGHYUN PARK,a,cANDY PENG XIANG,bFRANK FUXIANG MAO,a,bLI ZHANG,a CHUN-GUANG DI,bXIAO-MEI LIU,bYUAN SHAO,bBAO-FENG MA,bJAE-HYUN LEE,aKWON-SOO HA,c NOAH WALTON,a BRUCE T. LAHNa,b


摘要:

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.

下载 PDF 文件
  • 侧边栏广告 - 模式动物成功案例
  • 侧边栏广告 - 科研奖励基金计划
  • 侧边栏广告-积分兑换礼品