Open AccessNestin Is Required for the Proper Self‐Renewal of Neural Stem Cells
Author(s) -
Park Donghyun,
Xiang Andy Peng,
Mao Frank Fuxiang,
Zhang Li,
Di ChunGuang,
Liu XiaoMei,
Shao Yuan,
Ma BaoFeng,
Lee JaeHyun,
Ha KwonSoo,
Walton Noah,
Lahn Bruce T.
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.541
Subject(s) - nestin , biology , neural stem cell , microbiology and biotechnology , neuroepithelial cell , intermediate filament , embryonic stem cell , neurosphere , vimentin , stem cell , cytoskeleton , knockout mouse , neural tube , adult stem cell , cell , immunology , embryo , genetics , immunohistochemistry , receptor , gene
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