RT Journal Article
SR Electronic
T1 Myosin Heavy Chain-embryonic is a crucial regulator of skeletal muscle development and differentiation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 261685
DO 10.1101/261685
A1 Akashi Sharma
A1 Megha Agarwal
A1 Amit Kumar
A1 Pankaj Kumar
A1 Masum Saini
A1 Gabrielle Kardon
A1 Sam J. Mathew
YR 2018
UL http://biorxiv.org/content/early/2018/02/07/261685.abstract
AB Myosin heavy chains (MyHCs) are contractile proteins that are part of the thick filaments of the functional unit of the skeletal muscle, the sarcomere. In addition to MyHCs that are part of the adult muscle contractile network, two MyHCs - MyHC-embryonic and -perinatal are expressed during muscle development and are only transiently expressed in the adult during regeneration. The functions performed by these MyHCs has been a long-standing question and using a targeted mouse allele, we have characterized the role of MyHC-embryonic. Analysis of loss-of-function mice reveals that lack of MyHC-embryonic leads to mis-regulation of other MyHCs, alterations in fiber size, fiber number and fiber type at neonatal stages. We also find that loss of MyHC-embryonic leads to mis-regulation of genes involved in muscle differentiation. A broad theme from these studies is that loss of MyHC-embryonic has distinct effects on different muscles, possibly reflecting the unique fiber type composition of different muscles. Most significantly, our results indicate that MyHC-embryonic is required during embryonic and fetal myogenesis to regulate myogenic progenitor and myoblast differentiation in a non-cell autonomous manner via Mitogen Activated Protein Kinase (MAPKinase) and Fibroblast Growth Factor (FGF) signaling. Thus, our results signify that MyHC-embryonic is a key regulator of myogenic differentiation during embryonic, fetal and neonatal myogenesis.