Journal
DEVELOPMENTAL CELL
Volume 18, Issue 6, Pages 938-949Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2010.05.006
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Funding
- Fondation Leducq Transatlantic Network of Excellence, Associazione Italiana per la Ricerca sul Cancro, Association for International Cancer Research UK [07-0068]
- European Community [202213, 223098, NMP3-LA-2008-214402]
- Istituto Superiore di Sanita
- Italian Ministry of Health
- CARIPLO Foundation [2008.2463]
- Swedish Research Council
- Swedish Society for Medical Research
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The Wnt/beta-catenin pathway is evolutionary conserved signaling system that regulates cell differentiation and organogenesis. We show that endothelial specific stabilization of Wnt/beta-catenin signaling alters early vascular development in the embryo. The phenotype resembles that induced by upregulation of Notch signaling, including lack of vascular remodeling, altered elongation of the intersomitic vessels, defects in branching, and loss of venous identity. Both in vivo and in vitro data show that beta-catenin upregulates DII4 transcription and strongly increases Notch signaling in the endothelium, leading to functional and morphological alterations. The functional consequences of beta-catenin signaling depend on the stage of vascular development and are lost when a gain-of-function mutation is induced at a late stage of development or postnatally. Our findings establish a link between Wnt and Notch signaling in vascular development. We propose that early and sustained beta-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification.
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