Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 30, Pages 12064-12069Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1207210109
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology
- Astellas Foundation for Research on Metabolic Disorders
- Mitsubishi Pharma Research Foundation
- Miyata Cardiac Research Promotion Foundation
- Novartis Foundation (Japan) for the Promotion of Science
- Suzuken Memorial Foundation
- Takeda Science Foundation
- Mother and Child Health Foundation
- Naito Foundation
- Smoking Research Foundation
- Uehara Memorial Foundation
- Banyu Life Science International Foundation
- Ichiro Kanahara Foundation
- Nakatomi Foundation
- Japan Heart Foundation
- Ministry of Health, Labor and Welfare
- Grants-in-Aid for Scientific Research [23390274, 24790895] Funding Source: KAKEN
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available