Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis
Summary 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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2012-07-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/1/9/889 |
| _version_ | 1818652476520267776 |
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| author | Meikun Kan-O Ryu Takeya Takaya Abe Naoyuki Kitajima Motohiro Nishida Ryuji Tominaga Hitoshi Kurose Hideki Sumimoto |
| author_facet | Meikun Kan-O Ryu Takeya Takaya Abe Naoyuki Kitajima Motohiro Nishida Ryuji Tominaga Hitoshi Kurose Hideki Sumimoto |
| author_sort | Meikun Kan-O |
| collection | DOAJ |
| description | Summary
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. |
| first_indexed | 2024-12-17T02:22:37Z |
| format | Article |
| id | doaj.art-6f4eabfdcb74458ca3ea54b7695c962c |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T02:22:37Z |
| publishDate | 2012-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-6f4eabfdcb74458ca3ea54b7695c962c2022-12-21T22:07:13ZengThe Company of BiologistsBiology Open2046-63902012-07-011988989610.1242/bio.2012137020121370Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesisMeikun Kan-O0Ryu Takeya1Takaya Abe2Naoyuki Kitajima3Motohiro Nishida4Ryuji Tominaga5Hitoshi Kurose6Hideki Sumimoto7 Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan Department of Pharmacology and Toxicology, Kyushu University Graduate School of Pharmaceutical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Department of Pharmacology and Toxicology, Kyushu University Graduate School of Pharmaceutical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Department of Cardiovascular Surgery, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Department of Pharmacology and Toxicology, Kyushu University Graduate School of Pharmaceutical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Summary 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.http://bio.biologists.org/content/1/9/889ActinFhod3ForminMyofibrillogenesisSarcomere |
| spellingShingle | Meikun Kan-O Ryu Takeya Takaya Abe Naoyuki Kitajima Motohiro Nishida Ryuji Tominaga Hitoshi Kurose Hideki Sumimoto Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis Biology Open Actin Fhod3 Formin Myofibrillogenesis Sarcomere |
| title | Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis |
| title_full | Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis |
| title_fullStr | Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis |
| title_full_unstemmed | Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis |
| title_short | Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis |
| title_sort | mammalian formin fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis |
| topic | Actin Fhod3 Formin Myofibrillogenesis Sarcomere |
| url | http://bio.biologists.org/content/1/9/889 |
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