Effects of Growth Factors on Myogenic Differentiation

It has now been well established that the terminal differentiation of muscle cells in culture is subject to control by hormones and growth factors in the incubation medium. Thus far the most potent and most extensively studied agents are fibroblast growth factor (FGF), the insulinlike growth factors (IGFs), and transforming growth factor-beta (TGF-beta). Independent reports from several laboratories have established that both FGF and TGF-beta are potent inhibitors of differentiation and both appear to act at early stages of commitment to differentiation. Stimulation of differentiation by the IGFs (and by insulin at concentrations in the microgram/ml range) has also been observed and confirmed repeatedly. FGF and IGF are mitogenic for muscle cells, and TGF-beta either has no effect or suppresses cell proliferation, so previous generalizations that mitogens inhibit myogenic differentiation are clearly not valid when results with purified agents in well-defined media are considered. Work with oncogenes and specific toxins is beginning to reveal the mechanisms by which these agents might affect differentiation, and there is reason for optimism that an understanding of the molecular events that control terminal differentiation may be attained in the near future.