Genetic and epigenetic control of muscle development in vertebrates

The skeletal body muscle of vertebrates is derived from segmentally arranged mesodermal structures, the somites. Only the dorsal epithelial half of the somite, the dermomyotome, gives rise to muscle cells during normal development. Head muscle takes its origin from the somites, the unsegmented paraxial head mesoderm and the prechordal mesoderm. Some muscle precursor cells, for instance those for limb and tongue muscle, migrate over considerable distances before differentiating at their target sites. In recent years, our understanding of the molecular events underlying myogenesis has increased considerably. Muscle differentiation is preceded by several steps during which precursor cells are specified. Markers of myogenic specification are myf5, myoD, mrf4 and myogenin, which encode transcription factors of the basic helix-loop-helix family. These factors bind to promoters of many muscle-specific genes and interact with MEF2 (myocyte enhancer binding factor-2) belonging to the MADS (MCM1, agamous, deficiens, serum response factor) box transcription factors. Signalling events leading to myogenic precursor cell specification and to the formation of muscle fibres are being elucidated. Inductive signals emanate from the neural tube, notochord and ectoderm. Controversial findings concerning the role of the notochord and neural tube in muscle development suggest that the epigenetic events leading to myogenesis are more complex than originally anticipated. Signals from the lateral plate counteract those from the axial organs and induce the locally restricted emigration of muscle precursor cells. Future investigations will have to show how signalling molecules and their receptors interact in the process of fine-tuning muscle formation in the embryo.