4.8 Article

Tmem100, an ALK1 receptor signaling-dependent gene essential for arterial endothelium differentiation and vascular morphogenesis

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.1207210109

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资金

  1. Ministry of Education, Culture, Sports, Science, and Technology
  2. Astellas Foundation for Research on Metabolic Disorders
  3. Mitsubishi Pharma Research Foundation
  4. Miyata Cardiac Research Promotion Foundation
  5. Novartis Foundation (Japan) for the Promotion of Science
  6. Suzuken Memorial Foundation
  7. Takeda Science Foundation
  8. Mother and Child Health Foundation
  9. Naito Foundation
  10. Smoking Research Foundation
  11. Uehara Memorial Foundation
  12. Banyu Life Science International Foundation
  13. Ichiro Kanahara Foundation
  14. Nakatomi Foundation
  15. Japan Heart Foundation
  16. Ministry of Health, Labor and Welfare
  17. Grants-in-Aid for Scientific Research [23390274, 24790895] Funding Source: KAKEN

向作者/读者索取更多资源

Members of the transforming growth factor-beta superfamily play essential roles in various aspects of embryonic development and physiological organ function. Among them, bone morphogenetic protein (BMP) 9 and BMP10 regulate embryonic vascular development by activating their endothelial receptor ALK1 (activin receptor-like kinase 1, also called Acvrl1). ALK1-mediated intracellular signaling is implicated in the etiologies of human diseases, but their downstream functional proteins are largely unknown. In this study, we identified Tmem100, a gene encoding a previously uncharacterized intracellular transmembrane protein, to be an embryonic endothelium-enriched gene activated by BMP9 and BMP10 through the ALK1 receptor. Tmem100 null mice showed embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied most of the vascular abnormalities observed with the Acvrl1/Alk1 deficiency. The activity of Notch-and Akt-mediated signaling, which is essential for vascular development, was down-regulated in Tmem100 null mice. Cre-mediated deletion of Tmem100 in endothelial cells was sufficient to recapitulate the null phenotypes. These data indicated that TMEM100 may play indispensable roles downstream of BMP9/BMP10-ALK1 signaling during endothelial differentiation and vascular morphogenesis.

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