Open AccessMyosin heavy chain-embryonic regulates skeletal muscle differentiation during mammalian development
Author(s) -
Megha Agarwal,
Akashi Sharma,
Pankaj Kumar,
Amit Kumar,
Anushree Bharadwaj,
Masum Saini,
Gabrielle Kardon,
Sam J. Mathew
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.184507
Subject(s) - myogenesis , biology , myosin , microbiology and biotechnology , myocyte , progenitor cell , skeletal muscle , myod , cellular differentiation , fibroblast growth factor , myogenic regulatory factors , endocrinology , stem cell , genetics , gene , receptor
Myosin heavy chain-embryonic (MyHC-emb) is a skeletal muscle specific contractile protein expressed during muscle development. Mutations in MYH3, the gene encoding MyHC-emb leads to Freeman-Sheldon and Sheldon-Hall congenital contracture syndromes. Here, we characterize the role of MyHC-emb during mammalian development using targeted mouse alleles. Germline loss-of MyHC-emb leads to neonatal and postnatal alterations in muscle fiber size, fiber number, fiber type and mis-regulation of genes involved in muscle differentiation. Deletion of Myh3 during embryonic myogenesis leads to depletion of the myogenic progenitor cell pool and increase in the myoblast pool while fetal myogenesis-specific deletion of Myh3 causes depletion of both myogenic progenitor and myoblast pools. We uncover that the non-cell autonomous effect of MyHC-emb on myogenic progenitors and myoblasts are mediated by the fibroblast growth factor (FGF) signaling pathway and exogenous FGF rescues the myogenic differentiation defects upon loss of MyHC-emb function in vitro. Adult Myh3 null mice exhibit scoliosis, a characteristic phenotype exhibited by Freeman-Sheldon and Sheldon-Hall congenital contracture syndrome patients. Thus, we have identified MyHC-emb as a crucial myogenic regulator during development, performing dual cell autonomous and non-cell autonomous functions.