Research Summary

The role of developmental Myosin Heavy Chains in skeletal muscle development, regeneration, homeostasis and disease

This proposal is aimed at understanding the function and regulation of a key group of structural and contractile skeletal muscle proteins called myosin heavy chains (MyHCs). In order to understand MyHC gene function, I am focusing on 3 MyHCs called the developmental MyHCs (since they are expressed during development) which have roles in development, regeneration and homeostasis. The first key goal of this proposal is to generate conditional mouse alleles for these 3 MyHCs- MyHC-embryonic, -perinatal and -slow. The second key goal is to understand the independent and combinatorial functions of these 3 MyHCs during muscle development, differentiation and maturation in vivo. The third key goal is to use these MyHC alleles to test their role in muscle regeneration after injury and during disease as well as in skeletal muscle homeostasis. The fourth key goal is to understand the regulation of these MyHCs during myogenesis as well as to identify crucial signaling molecules and pathways that function to regulate them. The fifth key goal is to shed light on our understanding of diseases caused by mutations in these 3 MyHCs by studying the loss of function mouse models.

Figure Legend: Confocal maximum projection of a neonatal mouse hind limb cross section through the shank, labeled using immunofluorescence for laminin (green) marking the basement membrane, skeletal muscle myosin heavy chain slow (red) for slow muscle fibers, and DAPI (blue) for nuclei.