Author contributions: D.P. and A.P.X.: conception and design, provision of study material, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; F.F.M., L.Z., X.-M.L., Y.S., B.-F.M., C.-G.D., and J.H.L.: provision of study material, collection and assembly of data, data analysis and interpretation; K.-S.H.: provision of study material; N.W.: manuscript writing; B.T.L.: conception and design, provision of study material, data analysis and interpretation, manuscript writing, final approval of manuscript. D.P. and A.P.X. contributed equally to this article.
Tissue-Specific Stem Cells
Article first published online: 30 DEC 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 12, pages 2162–2171, December 2010
How to Cite
Park, D., Xiang, A. P., Mao, F. F., Zhang, L., Di, C.-G., Liu, X.-M., Shao, Y., Ma, B.-F., Lee, J.-H., Ha, K.-S., Walton, N. and Lahn, B. T. (2010), Nestin Is Required for the Proper Self-Renewal of Neural Stem Cells. STEM CELLS, 28: 2162–2171. doi: 10.1002/stem.541
First published online in STEM CELLS EXPRESS October 20, 2010; available online without subscription through the open access option.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 30 DEC 2010
- Article first published online: 30 DEC 2010
- Accepted manuscript online: 20 OCT 2010 02:17PM EST
- Manuscript Accepted: 27 AUG 2010
- Manuscript Received: 5 NOV 2009
- Human Frontier Science Program
- National Natural Science Foundation of China. Grant Number: 30671023
- National Basic Research Program of China. Grant Numbers: 2009CB522100, 2010CB945400
- Key Scientific and Technological Projects of Guangdong Province. Grant Number: 2007A032100003
- Intermediate filament;
- Neural stem cells
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