During mammalian muscle development, muscle progenitors called myoblasts fuse to make myofibres in two phases: embryonic and foetal. The myofibres are composed of contractile sarcomeres, a major component of which is myosin. While the functions of several transcriptional regulators of myogenesis have been intensively explored, relatively little is known about the roles of their downstream effectors such as the myosins. Furthermore, in the specific case of myosin heavy chain-embryonic (MyHC-emb, which is expressed in embryonic and foetal development), human mutations lead to congenital syndromes with a host of clinical symptoms, raising a question about their developmental origin. Now, Sam Mathew and colleagues address these issues using targeted alleles of mouse Myh3 (which encodes MyHC-emb). Half of Myh3Δ/Δ mutants die in utero, and those that survive show defects in myofibre number, area, weight and type. Myh3Δ/Δ mutants not only show mis-regulation of muscle differentiation genes, but also genes are specifically mis-regulated in certain muscle types. Conditional alleles reveal that MyHC-emb accelerates the differentiation of myogenic progenitors during both embryonic and foetal phases, even though it is expressed only in myofibres. This non-autonomous effect is also seen in vitro, where it is mediated by FGF signalling. Finally, surviving Myh3Δ/Δ mice have severe scoliosis, a phenotype seen in humans with MYH3 mutations. This study thus sheds new light on the complex roles of myosins in muscle development.
