Role of trophic factors in muscle differentiation

Muscle genes are developmentally regulated. In vivo, the differential expression of muscle structural genes during myogenesis is controlled in complex ways by extrinsic factors and by a pre-determined genetic program. Terminal differentiation, which is achieved when differentiated myoblasts fuse to form multi-nucleated myotubes, appears mainly regulated by intrinsic factors. Environmental components, on the other hand, play a significant role in the developmental regulation of genes during the course of muscle fiber maturation. In culture, the differential expression of muscle genes is assumed to be solely controlled by intrinsic genetic factors, in the sense that, once precursors cease to proliferate and are committed to become myoblasts, they inevitably progress through terminal differentiation, whatever the environment. The system lacks the necessary elements to proceed towards fiber maturation. Consequently, muscle culture models have, until recently, been limited in studies dealing with the roles played both by genetic and environmental factors in the regulation of muscle gene expression. The accumulating data, however, suggest that under given culture conditions, it is becoming possible to make cells mature beyond embryonic stages and express specific phenotypes in response to extrinsic factors. This paper reviews some of the progress in the development of culture systems which will be useful in studies of muscle plasticity.