Molecular dynamics to restore/remodel neuromuscular connections during muscle growth and regeneration

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Successful regeneration and remodeling of the neuromuscular connections are critical for restoring functional properties of contractile physiology of muscle fibers. While the spatiotemporal regulatory mechanisms coordinating these processes with myogenesis itself remain unclear, various neural factors including attractive and repulsive axon-guidance cue ligands and their receptors may be involved. Recently, we found that satellite cells, resident myogenic stem cells normally positioned beneath the basal lamina of mature muscle fibers, up-regulate a secreted neural chemorepellent semaphorin 3A (Sema3A) during early-differentiation period, upon acute muscle injury in vivo(Tatsumi et al., 2009). The current study encouraged the possible regulation of Sema3A expression by time-coordinated prevalence of extracellular up-regulator (HGF and FGF2) and down-regulator (TGF-β3) concentrations bathing differentiating satellite cells (myoblasts) in regenerating muscle tissue. By understanding this growth factor ligand-driving scenario, we will be able to design new procedures that specifically target regenerative motoneuritogenesis to ensure muscle growth and repair, contributing to the meat-animal production and human sports and health sciences aimed to enhance physical performance and medical therapies for neuromuscular disorders and age-related muscle atrophy