Fhod3 knockout in mice resulted in embryonic lethality by day 11.5 due to a failure of premyofibrils to mature, demonstrating its essential role in sarcomere organization during heart development.
The mammalian formin Fhod3 is essential for actin filament assembly and sarcomere organization during early heart development.
Heart development requires organized integration of actin filaments into the sarcomere, the contractile unit of myofibrils, although it remains largely unknown how actin filaments are assembled during myofibrillogenesis. Here we show that Fhod3, a member of the formin family of proteins that play pivotal roles in actin filament assembly, is essential for myofibrillogenesis at an early stage of heart development. Fhod3(-/-) mice appear normal up to embryonic day (E) 8.5, when the developing heart, composed of premyofibrils, initiates spontaneous contraction. However, these premyofibrils fail to mature and myocardial development does not continue, leading to embryonic lethality by E11.5. Transgenic expression of wild-type Fhod3 in the heart restores myofibril maturation and cardiomyogenesis, which allow Fhod3(-/-) embryos to develop further. Moreover, cardiomyopathic changes with immature myofibrils are caused in mice overexpressing a mutant Fhod3, defective in binding to actin. These findings indicate that actin dynamics, regulated by Fhod3, participate in sarcomere organization during myofibrillogenesis and thus play a crucial role in heart development.
Kan-o et al. (Wed,) conducted a other in Cardiogenesis and embryonic heart development. Fhod3 gene knockout vs. Wild-type mice was evaluated on Embryonic lethality and myofibril maturation. Fhod3 knockout in mice resulted in embryonic lethality by day 11.5 due to a failure of premyofibrils to mature, demonstrating its essential role in sarcomere organization during heart development.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: