Megf10 deficiency impairs skeletal muscle stem cell migration and muscle regeneration

FEBS Open Bio. 2021 Jan;11(1):114-123. doi: 10.1002/2211-5463.13031. Epub 2020 Nov 26.

Abstract

Biallelic loss-of-function MEGF10 mutations lead to MEGF10 myopathy, also known as early onset myopathy with areflexia, respiratory distress, and dysphagia (EMARDD). MEGF10 is expressed in muscle satellite cells, but the contribution of satellite cell dysfunction to MEGF10 myopathy is unclear. Myofibers and satellite cells were isolated and examined from Megf10-/- and wild-type mice. A separate set of mice underwent repeated intramuscular barium chloride injections. Megf10-/- muscle satellite cells showed reduced proliferation and migration, while Megf10-/- mouse skeletal muscles showed impaired regeneration. Megf10 deficiency is associated with impaired muscle regeneration, due in part to defects in satellite cell function. Efforts to rescue Megf10 deficiency will have therapeutic implications for MEGF10 myopathy and other inherited muscle diseases involving impaired muscle regeneration.

Keywords: MEGF10 myopathy; satellite cells; skeletal muscle regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Humans
  • Loss of Function Mutation
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Knockout
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / pathology*
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology
  • Regeneration / genetics*
  • Satellite Cells, Skeletal Muscle / pathology

Substances

  • Megf10 protein, mouse
  • Membrane Proteins