The Wnt/β-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/notch signaling

Monica Corada, Daniel Nyqvist, Fabrizio Orsenigo, Andrea Caprini, Costanza Giampietro, Makoto M. Taketo, M. Luisa Iruela-Arispe, Ralf H. Adams, Elisabetta Dejana*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

Abstract

The Wnt/β-catenin pathway is evolutionary conserved signaling system that regulates cell differentiation and organogenesis. We show that endothelial specific stabilization of Wnt/β-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 showthat β-catenin upregulates Dll4 transcription and strongly increases Notch signaling in the endothelium, leading to functional and morphological alterations. The functional consequences of β-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 β-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification.

Original languageEnglish (US)
Pages (from-to)938-949
Number of pages12
JournalDevelopmental Cell
Volume18
Issue number6
DOIs
StatePublished - Mar 16 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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