Enhanced expression of mouse c-ski accompanies terminal skeletal muscle differentiation in vivo and in vitro.

Overexpression of either v-ski, or the proto-oncogene, c-ski, in quail embryo fibroblasts induces the expression of myoD and myogenin, converting the cells to myoblasts capable of differentiating into skeletal myotubes. In transgenic mice, overexpression of ski also influences muscle development, but in this case it effects fully formed muscle, causing hypertrophy of fast skeletal muscle fibers. In attempts to determine whether endogenous mouse c-ski plays a role in either early muscle cell determination or late muscle cell differentiation, we analyzed mRNA expression during muscle development in mouse embryos and during in vitro terminal differentiation of skeletal myoblasts. To generate probes for these studies we cloned coding and 3' non-coding regions of mouse c-ski. In situ hybridization revealed low c-ski expression in somites, and only detected elevated levels of mRNA in skeletal muscle beginning at about 12.5 days of gestation. Northern analysis revealed a two-fold increase in c-ski mRNA during terminal differentiation of skeletal muscle cell lines in vitro. Our results suggest that c-ski plays a role in terminal differentiation of skeletal muscle cells not in the determination of cells to the myogenic lineage.