The Myogenic Factor Myf5 Supports Efficient Skeletal Muscle Regeneration by Enabling Transient Myoblast Amplification

¹ Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, Parkstrasse 1, 61231 Bad Nauheim, Germany
² Section of Gene Function and Regulation, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK

^* To whom correspondence should be addressed. E-mail: thomas.braun{at}kerckhoff.mpg.de.

	Abstract

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 of 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 four weeks after injury. Although we did not detect a striking reduction of MyoD positive activated myoblasts and 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 six and seven days of culture. We reason that Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification.

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