MyoD is required for myogenic stem cell function in adult skeletal muscle.
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.
Megeney
L A
LA
Institute for Molecular Biology and Biotechnology, Cancer Research Group, McMaster University, Hamilton, Ontario, Canada.
Kablar
B
B
Garrett
K
K
Anderson
J E
JE
Rudnicki
M A
MA
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D017570:MyoD Protein / Q000235:genetics / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology
D016189:Dystrophin; D017570:MyoD Protein