Nestin is required for the proper self-renewal of 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.
Department of Human Genetics, University of Chicago, Howard Hughes Medical Institute, Chicago, Illinois, USA. donghyun@uchicago.edu
Donghyun
D
Park
Andy Peng
AP
Xiang
Frank Fuxiang
FF
Mao
Li
L
Zhang
Chun-Guang
CG
Di
Xiao-Mei
XM
Liu
Yuan
Y
Shao
Bao-Feng
BF
Ma
Jae-Hyun
JH
Lee
Kwon-Soo
KS
Ha
Noah
N
Walton
Bruce T
BT
Lahn
D000818:Animals; D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D020964:Embryo Loss / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018390:Gene Targeting; D007381:Intermediate Filament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D054259:Neural Tube / Q000378:metabolism / Q000473:pathology; D010641:Phenotype
D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin