FGF6 modulates the expression of fibroblast growth factor receptors and myogenic genes in muscle cells.

Fgf6 is the only known member of the FGF family whose expression is restricted to the muscle cell lineage during development, suggesting it may have a role in myogenesis. Muscle satellite cells but not C2 myoblast cells were found to express Fgf6. We have used purified recombinant FGF6 protein to explore the effect of this factor on C2 cells in culture. FGF6 stimulated the proliferation of C2 myoblasts and, in combination with heparin, induced their morphological transformation. FGF6, added at 5 ng/ml and in the presence of heparin, increased the expression of a subset of muscle cell differentiation markers. In contrast, at 25 ng/ml, it down-regulated the expression of myogenic markers and myogenic transcription factors examined and delayed differentiation into myotubes of C2 cells. It also up-regulated the expression of FgfR1 and had an opposite effect on FgfR4. These results suggest that intramuscular FGF6 concentrations could influence the proliferation and differentiation processes taking place during development.