Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis

Meikun Kan-O, Ryu Takeya, Takaya Abe, Naoyuki Kitajima, Motohiro Nishida, Ryuji Tominaga, Hitoshi Kurose, Hideki Sumimoto

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)889-896
Number of pages8
JournalBiology Open
Volume1
Issue number9
DOIs
Publication statusPublished - Sep 15 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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