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Myosin Heavy Chain-embryonic is a crucial regulator of skeletal muscle development and differentiation.

Akashi Sharma, Megha Agarwal, Amit Kumar, Pankaj Kumar, Masum Saini, Gabrielle Kardon, Sam Mathew
doi: https://doi.org/10.1101/261685
Akashi Sharma
Regional Centre for Biotechnology;
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Megha Agarwal
Regional Centre for Biotechnology;
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Amit Kumar
David Geffen School of Medicine, UCLA;
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Pankaj Kumar
Regional Centre for Biotechnology;
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Masum Saini
Regional Centre for Biotechnology;
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Gabrielle Kardon
University of Utah
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Sam Mathew
Regional Centre for Biotechnology;
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  • For correspondence: sjmathew@rcb.res.in
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Abstract

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.

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Posted February 07, 2018.
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Myosin Heavy Chain-embryonic is a crucial regulator of skeletal muscle development and differentiation.
Akashi Sharma, Megha Agarwal, Amit Kumar, Pankaj Kumar, Masum Saini, Gabrielle Kardon, Sam Mathew
bioRxiv 261685; doi: https://doi.org/10.1101/261685
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Myosin Heavy Chain-embryonic is a crucial regulator of skeletal muscle development and differentiation.
Akashi Sharma, Megha Agarwal, Amit Kumar, Pankaj Kumar, Masum Saini, Gabrielle Kardon, Sam Mathew
bioRxiv 261685; doi: https://doi.org/10.1101/261685

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