Ca²⁺ as a coordinator of skeletal muscle differentiation, fusion and contraction

Muscle regeneration is essential for vertebrate muscle homeostasis and recovery after injury. During regeneration, muscle stem cells differentiate into myocytes, which then fuse with pre-existing muscle fibers. Hence, differentiation, fusion and contraction must be tightly regulated during regeneration to avoid the disastrous consequences of premature fusion of myocytes to actively contracting fibers. Cytosolic calcium (Ca2+), which is coupled to both induction of myogenic differentiation and contraction, has more recently been implicated in the regulation of myocyte-to-myotube fusion. In this Viewpoint, we propose that Ca2+-mediated coordination of differentiation, fusion, and contraction is a feature selected in the amniotes to facilitate muscle regeneration.