MyoD is required for myogenic stem cell function in adult skeletal muscle.

Abstract

To investigate the function of MyoD in adult skeletal muscle, we interbred MyoD mutant mice with mdx mice, a model for Duchenne and Becker muscular dystrophy. Mice lacking both MyoD and dystrophin displayed a marked increase in severity of myopathy leading to premature death, suggesting a role for MyoD in muscle regeneration. Examination of MyoD mutant muscle revealed elevated numbers of myogenic cells; however, myoblasts derived from these cells displayed normal differentiation potential in vitro. Following injury, MyoD mutant muscle was severely deficient in regenerative ability, and we observed a striking reduction in the in vivo proliferation of myogenic cells during regeneration. Therefore, we propose that the failure of MyoD-deficient muscle to regenerate efficiently is not caused by a reduction in numbers of satellite cells, the stem cells of adult skeletal muscle, but results from an increased propensity for stem-cell self-renewal rather than progression through the myogenic program.