Abstract
Developing skeletal muscles express unique myosin isoforms, including embryonic and neonatal myosin heavy chains, coded by the myosin heavy chain 3 (MYH3) and MYH8 genes, respectively, and myosin light chain 1 embryonic/atrial, encoded by the myosin light chain 4 (MYL4) gene. These myosin isoforms are transiently expressed during embryonic and fetal development and disappear shortly after birth when adult fast and slow myosins become prevalent. However, developmental myosins persist throughout adult stages in specialized muscles, such as the extraocular and jaw-closing muscles, and in the intrafusal fibers of the muscle spindles. These myosins are re-expressed during muscle regeneration and provide a specific marker of regenerating fibers in the pathologic skeletal muscle. Mutations in MYH3 or MYH8 are responsible for distal arthrogryposis syndromes, characterized by congenital joint contractures and orofacial dysmorphisms, supporting the importance of muscle contractile activity and body movements in joint development and in shaping the form of the face during fetal development. The biochemical and biophysical properties of developmental myosins have only partially been defined, and their functional significance is not yet clear. One possibility is that these myosins are specialized in contracting against low loads, and thus, they may be adapted to the prenatal environment, when fetal muscles contract against a very low load compared to postnatal muscles.
Highlights
Sarcomeric myosins present in mammalian striated muscle are class II or conventional myosins, each myosin molecule consisting of two heavy chains (MyHCs), two essential light chains (MLCs), and two regulatory myosin light chain (MLC)
Full list of author information is available at the end of the article and neonatal myosins, coded by myosin heavy chain 3 (MYH3) and MYH8, respectively, and myosin light chain 1 embryonic/atrial, coded by the myosin light chain 4 (MYL4) gene, which are present at high levels in the initial stages of muscle development, are downregulated after birth, and are reexpressed during muscle regeneration
In situ hybridization studies showed that the transcripts for MLC-1emb (MYL4) are expressed together with MLC-1fast beginning in the early developmental stages in the mouse embryonic skeletal muscle; their relative levels are similar at E12.5 but MLC-1fast becomes predominant at E15.5 [16]
Summary
Sarcomeric myosins present in mammalian striated muscle are class II or conventional myosins, each myosin molecule consisting of two heavy chains (MyHCs), two essential light chains (MLCs), and two regulatory MLCs. Most of these genes are expressed in the developing skeletal muscle, including two MyHC isoforms, called embryonic Full list of author information is available at the end of the article and neonatal (or perinatal) myosins, coded by MYH3 and MYH8, respectively, and myosin light chain 1 embryonic/atrial, coded by the MYL4 gene, which are present at high levels in the initial stages of muscle development, are downregulated after birth, and are reexpressed during muscle regeneration.
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