The myogenic factor Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification.
The myogenic factor Myf5 defines the onset of myogenesis in mammals during development. Mice lacking both Myf5 and MyoD fail to form myoblasts and are characterized by a complete absence of skeletal muscle at birth. To investigate the function of Myf5 in adult skeletal muscle, we generated Myf5 and mdx compound mutants, which are characterized by constant regeneration. Double mutant mice show an increase of dystrophic changes in the musculature, although these mice were viable and the degree of myopathy was modest. Myf5 mutant muscles show a small decrease in the number of muscle satellite cells, which was within the range of physiological variations. We also observed a significant delay in the regeneration of Myf5 deficient skeletal muscles after injury. Interestingly, Myf5 deficient skeletal muscles were able to even out this flaw during the course of regeneration, generating intact muscles 4 weeks after injury. Although we did not detect a striking reduction of MyoD positive activated myoblasts or of Myf5-LacZ positive cells in regenerating muscles, a clear decrease in the proliferation rate of satellite cell-derived myoblasts was apparent in satellite cell-derived cultures. The reduction of the proliferation rate of Myf5 mutant myoblasts was also reflected by a delayed transition from proliferation to differentiation, resulting in a reduced number of myotube nuclei after 6 and 7 days of culture. We reason that Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification. Disclosure of potential conflicts of interest is found at the end of this article.
Ustanina
Svetlana
S
Max Planck Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, Parkstrasse 1, Bad Nauheim, Germany.
Carvajal
Jaime
J
Rigby
Peter
P
Braun
Thomas
T
D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D048429:Cell Size; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D009136:Muscular Dystrophies / Q000235:genetics; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology
C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; C063403:myogenic factor 6