The role of the IGFs in myogenic differentiation.

Of the three families of growth factors/hormones (the FGFs, TGF-betas, and IGFs) that have major effects on the differentiation of skeletal muscle cells, only the IGFs stimulate the process; indeed, the IGFs are the only well-defined agents thus far shown to stimulate myogenesis. All of these agents affect the expression of myogenin, one of the recently discovered family of myogenesis controlling genes, and TGF-beta and FGF inhibit the expression of MyoD1 as well. (L6 cells do not express MyoD1, so we have not looked for an effect of IGFs on it.) At least partly as a result of this action, these agents inhibit or stimulate all aspects of myogenic differentiation--fusion, expression of a set of muscle-specific proteins, and attainment of a postmitotic state--in all tested cell lines and primary muscle cell cultures. It is becoming clear that the myogenic controlling genes are capable of regulating expression of genes for the entire family of muscle specific proteins, so the principal question remaining about actions of these growth factors is the mechanism by which they inhibit or induce expression of the myogenin or MyoD1 genes. In spite of the uncertainty about their interactions, the discovery of the myogenesis controlling genes now provides a much sharper focus for studies on the processes involved in terminal differentiation of skeletal muscle cells. The demonstration that expression of these genes is controlled, both positively and negatively, by specific growth factors that are now readily available opens exciting new possibilities in endocrinology and developmental biology.