Fhod3 in zebrafish supports myofibril stability during growth of embryonic skeletal muscle

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Abstract
Background: Actin filament organization in cardiomyocytes critically depends on the formin Fhod3, but a role for Fhod3 in skeletal muscle development has not yet been described. Results: We demonstrate here that in zebrafish mutated for one of two fhod3 paralog genes, fhod3a , skeletal muscle of the trunk appears normal through 2 days post-fertilization, but afterward exhibits myofibril damage, including gaps between myofibrils and myofibril fragmentation. Despite the apparent progressive nature of myofibril damage, fhod3a mutant embryos differ from muscular dystrophy models in that damage is exacerbated by inhibition of muscle activity, and fhod3a mutants show no evidence of sarcolemma disruption. Rather, our results suggest myofibril damage coincides with growth of the skeletal muscle fiber contractile apparatus. We find that neither the second fhod3 paralog, fhod3b , nor the related fhod1 contribute to embryonic skeletal muscle development, but simultaneous mutation of fhod3a and fhod3b was associated with pericardial edema suggestive of cardiac dysfunction. Conclusions: Taken together, these results indicate fhod3- encoded formins are dispensable for initial myofibril assembly in skeletal muscle, but promote myofibril stability during muscle fiber growth. This is the first demonstration that Fhod3 contributes to skeletal muscle development in a vertebrate.
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Funding Information
  • France Hendricks Foundation (1743391)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD099031)

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