Novel approaches to analyze the regulatory mechanisms of cardiovascular genes in development and morphogenesis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15407
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine
• Research Institution: National Cardiovascular Center Research Institute
• 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)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 心血管発生 / シグナル伝達 / 遺伝子発現調節

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.

Free Research Field

血管生物学　発生学　周産期・新生児医学