Nestin is required for the proper self-renewal of neural stem cells.
Stem Cells
; 28(12): 2162-71, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20963821
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Células-Tronco Neurais
/
Proteínas de Filamentos Intermediários
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Revista:
Stem Cells
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos