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

BACKGROUND

Actin filament organization in cardiomyocytes critically depends on the formin Fhod3, but no role has been previously described for Fhod3 in skeletal muscle development.

RESULTS

We demonstrate here that in zebrafish mutated for one of two paralog genes, , skeletal muscle of the trunk appears normal through 2 days post-fertilization, but afterward exhibits myofibril damage, including gaps between myofibrils and myofibril fragmentation. Although myofibril damage appears progressive, mutant embryos differ from muscular dystrophy models in that damage is not activity-dependent, but is exacerbated by inhibition of muscle activity. Moreover, mutants show no evidence of sarcolemma disruption. Rather, our results suggest myofibril damage coincides with growth of the skeletal muscle fiber contractile apparatus. Neither the second paralog, , nor the more distantly related appear to contribute to embryonic skeletal muscle development, but simultaneous mutation of and was associated with pericardial edema suggestive of cardiac dysfunction.

CONCLUSIONS

Taken together, these results indicate a homolog is dispensable for initial myofibril assembly in skeletal muscle, but promotes myofibril stability during muscle fiber growth. This is the first demonstration that Fhod3 contributes to skeletal muscle development in a vertebrate.