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Publication : The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling.

First Author  Corada M Year  2010
Journal  Dev Cell Volume  18
Issue  6 Pages  938-49
PubMed ID  20627076 Mgi Jnum  J:163848
Mgi Id  MGI:4830037 Doi  10.1016/j.devcel.2010.05.006
Citation  Corada M, et al. (2010) The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Dev Cell 18(6):938-49
abstractText  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 Dll4 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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