A role for the myogenic determination gene Myf5 in adult regenerative myogenesis.
The myogenic determination genes Myf5, Myod and Mrf4 direct skeletal muscle cell fate prenatally. In adult myogenesis, Myod has been shown to regulate myoblast differentiation, however, our understanding of satellite cell regulation is incomplete since the roles of Myf5 and Mrf4 had not been clearly defined. Here we examine the function of Myf5 and Mrf4 in the adult using recently generated alleles. Mrf4 is not expressed in normal or Myf5 null satellite cells and myoblasts, therefore excluding a role for this determination gene in adult muscle progenitors. Skeletal muscles of adult Myf5 null mice exhibit a subtle progressive myopathy. Crucially, adult Myf5 null mice exhibit perturbed muscle regeneration with a significant increase in muscle fibre hypertrophy, delayed differentiation, adipocyte accumulation, and fibrosis after freeze-injury. Satellite cell numbers are not significantly altered in Myf5 null animals and they show a modest impaired proliferation under some conditions in vitro. Mice double mutant for Myf5 and Dystrophin were more severely affected than single mutants, with enhanced necrosis and regeneration. Therefore, we show that Myf5 is a regulator of regenerative myogenesis and homeostasis, with functions distinct from those of Myod and Mrf4.
Gayraud-Morel
Barbara
B
Stem Cells and Development, Dept. of Developmental Biology, Pasteur Institute, CNRS URA 2578, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Chrétien
Fabrice
F
Flamant
Patricia
P
Gomès
Danielle
D
Zammit
Peter S
PS
Tajbakhsh
Shahragim
S
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000502:physiology*; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics* / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology
C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; C063403:myogenic factor 6