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Department of Cancer Biology, Research Institute, The Cleveland
Clinic Foundation, Cleveland, Ohio 44195 USA
The c-ski proto-oncogene has been implicated in the
control of cell growth and skeletal muscle differentiation. To
determine its normal functions in vivo, we have disrupted the mouse
c-ski gene. Our results show a novel role for ski in
the morphogenesis of craniofacial structures and the central nervous
system, and confirm its proposed function as a player in skeletal
muscle development. Homozygous mutant mice show perinatal lethality
resulting from exencephaly, a defect caused by failed closure of the
cranial neural tube during neurulation. The timing of the neural tube defect in ski 
/ embryos coincides with
excessive apoptosis in the cranial neuroepithelium, as well as in the
cranial mesenchyme. Homozygous ski mutants also exhibit a
dramatic reduction in skeletal muscle mass, consistent with a defect in
expansion of a myogenic precursor population. Nestin is an intermediate
filament expressed in highly proliferative neuroepithelial stem cells
and in myogenic precursors. Interestingly, we find decreased nestin
expression in both the cranial neural tube and the somites of
ski / embryos, compared with their normal
littermates, but no reduction of nestin in the caudal neural tube.
These results are consistent with a model in which ski
activities are required for the successful expansion of a subset of
precursors in the neuroepithelial or skeletal muscle lineages.
[Key Words: ski proto-oncogene; nestin; neural tube]
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