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Park, D, Xiang, AP, Mao, FF, Zhang, L, Di, CG, Liu, XM, Shao, Y, Ma, BF, Lee, JH, Ha, KS, Walton, N and Lahn, BT (2010) Nestin is required for the proper self-renewal of neural stem cells. Stem Cells 28:2162-71


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.


PubMed Online version:10.1002/stem.541


Animals; Cell Death; Cell Proliferation; Cell Survival; Cells, Cultured; Cytoskeleton/metabolism; Embryo Loss/metabolism; Embryo Loss/pathology; Embryo, Mammalian/metabolism; Embryo, Mammalian/pathology; Gene Deletion; Gene Expression Regulation; Gene Targeting; Intermediate Filament Proteins/deficiency; Intermediate Filament Proteins/genetics; Intermediate Filament Proteins/metabolism; Mice; Nerve Tissue Proteins/deficiency; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neural Stem Cells/cytology; Neural Stem Cells/metabolism; Neural Tube/metabolism; Neural Tube/pathology; Phenotype



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status



GO:0043524: negative regulation of neuron apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion



  • regulates_o_occurs_in:(CL:0000047)

Seeded From UniProt


See also


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