Novel approaches to analyze the regulatory mechanisms of cardiovascular genes in development and morphogenesis
| Project/Area Number |
15K15407
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
NAKAGAWA Osamu 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (40283593)
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| Co-Investigator(Kenkyū-buntansha) |
坂部 正英 奈良県立医科大学, 医学部, 助教 (00525983)
久光 隆 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (50327946)
西谷 友重 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (50393244)
岩田 裕子 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (80171908)
渡邉 裕介 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (20562333)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 心血管発生 / シグナル伝達 / 遺伝子発現調節 / 心血管発生・形態形成 / 転写調節 / 血管内皮細胞 / 形態形成 / 血管内皮 |
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| Outline of Final Research Achievements |
Bone morphogenetic protein 9 (BMP9)/BMP10-ALK1 receptor signaling is essential for endothelial differentiation and vascular morphogenesis. Mutations in ALK1/ACVRL1 are implicated in human vascular diseases, and the Alk1/Acvrl1 deletion causes impaired vascular formation and embryonic lethality in mice. We previously identified Tmem100 to be an endothelium-enriched gene activated by the ALK1 signaling. Tmem100 null mice showed embryonic lethality due to the defects of vascular morphogenesis. In this study, we introduced novel experimental approaches using CRISPR/Cas9 gene editing and bacterial artificial chromosome-based distant enhancer reporters. In transgenic mouse analysis, we narrowed down the Tmem100 enhancer region for embryonic vascular expression, which showed characteristic activity in a subset of arterial endothelial cells. Further studies are ongoing in our laboratory to clarify the significance of Tmem100 in vascular development and disease.
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Report
(3 results)
Research Products
(11 results)
