The role of semaphorin3A in myogenic regeneration and the formation of functional neuromuscular junctions on new fibres

Current research on skeletal muscle injury and regeneration highlights the crucial role of nerve–muscle interaction in the restoration of innervation during that process. Activities of muscle satellite or stem cells, recognized as the ‘currency’ of myogenic repair, have a pivotal role in these events, as shown by ongoing research. More recent investigation of myogenic signalling events reveals intriguing roles for semaphorin3A (Sema3A), secreted by activated satellite cells, in the muscle environment during development and regeneration. For example, Sema3A makes important contributions to regulating the formation of blood vessels, balancing bone formation and bone remodelling, and inflammation, and was recently implicated in the establishment of fibre-type distribution through effects on myosin heavy chain gene expression. This review highlights the active or potential contributions of satellite-cell-derived Sema3A to regulation of the processes of motor neurite ingrowth into a regenerating muscle bed. Successful restoration of functional innervation during muscle repair is essential; this review emphasizes the integrative role of satellite-cell biology in the progressive coordination of adaptive cellular and tissue responses during the injury-repair process in voluntary muscle.