Genetic and epigenetic control of skeletal muscle development.

In recent years our understanding of the molecular processes underlying skeletal myogenesis has improved considerably. Overt myogenesis is preceded by a number of steps leading to the specification of muscle precursor cells. During this period, myogenic precursors express mRNAs for Muscle Regulatory Factors (MRFs) of the bHLH-family of transcription factors: MyoD, Myf5, Myogenin and MRF4. These factors are specific for developing skeletal muscle and their identification belongs to the great achievements in muscle research. Other transcriptional regulators involved in myogenesis are Pax3 and Pax7, as well as the myocyte enhancer factors (MEFs), especially MEF2. Other inhibitory transcription factors may interact with histones to render muscle-specific genes inacessible. More recently, signaling events involving the Wnt-glycoproteins and Sonic Hedgehog have been identified that lead to the induction or expansion of muscle-specific genes during embryogenesis. Sources of these signals were identified to be the neural tube, ectoderm and notochord. Interestingly, a bias towards muscle differentiation already resides in cells of the epiblast. Thus, it can be reasoned that muscle differentiation does not have to be induced, but maybe just derepressed. Apart from inductive or permissive signals involved in differentiation control, other signalling events have been described leading to the definite arrangement of muscle groups in the body. These processes involve the changes in the cytoskeleton, delay of differentiation, cell migration and target recognition.