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, conve rting the cells to myoblasts capable of differentiating into skeletal myotubes. In transgenic mice, overexpression of ski also influences mu scle development, but in this case it effects fully formed muscle, cau sing hypertrophy of fast skeletal muscle fibers. In attempts to determ ine whether endogenous mouse c-ski plays a role in either early muscle cell determination or late muscle cell differentiation, we analyzed m RNA expression during muscle development in mouse embryos and during i n vitro terminal differentiation of skeletal myoblasts. To generate pr obes for these studies we cloned coding and 3' non-coding regions of m ouse c-ski. In situ hybridization revealed low c-ski expression in som ites, and only detected elevated levels of mRNA in skeletal muscle beg inning at about 12.5 days of gestation. Northern analysis revealed a t wo-fold increase in c-ski mRNA during terminal differentiation of skel etal 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. (C) 1995 Wiley-Liss, Inc.