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PMID: 10428027 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis.

Cell ·Vol. 98 ·No. 2 ·1999-07-23 ·Pages 147-57

Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oosthuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter MC, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert JM, Collen D, Dejana E

Abstract

Vascular endothelial cadherin, VE-cadherin, mediates adhesion between endothelial cells and may affect vascular morphogenesis via intracellular signaling, but the nature of these signals remains unknown. Here, targeted inactivation (VEC-/-) or truncation of the beta-catenin-binding cytosolic domain (VECdeltaC/deltaC) of the VE-cadherin gene was found not to affect assembly of endothelial cells in vascular plexi, but to impair their subsequent remodeling and maturation, causing lethality at 9.5 days of gestation. Deficiency or truncation of VE-cadherin induced endothelial apoptosis and abolished transmission of the endothelial survival signal by VEGF-A to Akt kinase and Bcl2 via reduced complex formation with VEGF receptor-2, beta-catenin, and phosphoinositide 3 (PI3)-kinase. Thus, VE-cadherin/ beta-catenin signaling controls endothelial survival.

MeSH Terms

Animals Antigens, CD Apoptosis/physiology Cadherins/genetics Cell Survival/physiology Cytoskeletal Proteins/physiology Cytosol/chemistry,physiology DNA Primers Endothelial Growth Factors/physiology Endothelium, Vascular/chemistry,cytology,ultrastructure Fetus/cytology Gene Expression Regulation, Developmental Hematopoiesis/physiology In Situ Nick-End Labeling Intercellular Junctions/physiology Lymphokines/physiology Mice Mice, Transgenic Microscopy, Electron Mutagenesis, Site-Directed Neovascularization, Physiologic/physiology Phosphatidylinositol 3-Kinases/metabolism Receptor Protein-Tyrosine Kinases/physiology Receptors, Growth Factor/physiology Receptors, Vascular Endothelial Growth Factor Signal Transduction/physiology Trans-Activators Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors beta Catenin

Chemicals

Antigens, CD CTNNB1 protein, mouse Cadherins Cytoskeletal Proteins DNA Primers Endothelial Growth Factors Lymphokines Receptors, Growth Factor Trans-Activators Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors beta Catenin cadherin 5 Phosphatidylinositol 3-Kinases Receptor Protein-Tyrosine Kinases Receptors, Vascular Endothelial Growth Factor

Authors & Affiliations

23 authors, click to expand affiliations / ORCID

Carmeliet P

Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium. peter.carmelilet@med.kuleuven.ac.be

Lampugnani M G

Moons L

Breviario F

Compernolle V

Bono F

Balconi G

Spagnuolo R

Oosthuyse B

Dewerchin M

Zanetti A

Angellilo A

Mattot V

Nuyens D

Lutgens E

Clotman F

de Ruiter M C

Gittenberger-de Groot A

Poelmann R

Lupu F

Herbert J M

Collen D

Dejana E

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)81010-7

peter.carmelilet@med.kuleuven.ac.be

Published

1999-07-23

Pages

147-57

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/s0092-8674(00)81010-7 View journal details

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Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis.

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