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Published 15 September 2003. doi:10.1083/jcb.200212157
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© The Rockefeller University Press, 0021-9525/2003/9/1111 $5.00
The Journal of Cell Biology, Volume 162, Number 6, 1111-1122

Article

 The conditional inactivation of the ß-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility

Anna Cattelino1,2, Stefan Liebner1, Radiosa Gallini1, Adriana Zanetti2, Giovanna Balconi2, Alessandro Corsi3, Paolo Bianco3, Hartwig Wolburg4, Robert Moore5, Boussadia Oreda5, Rolf Kemler5 and Elisabetta Dejana1,2,6

1 FIRC Institute of Molecular Oncology, 20139 Milan, Italy
2 Mario Negri Institute for Pharmacological Research, 20157 Milan, Italy
3 Department of Experimental Medicine and Pathology, University La Sapienza, 00185 Rome, Italy
4 Institute of Pathology, University of Tübingen, D-72076 Tübingen, Germany
5 Max Planck Institute of Immunology, 79108 Freiburg, Germany
6 Department of Genetics, University of Milan, 20122 Milan, Italy

Address correspondence to Elisabetta Dejana, FIRC Institute of Molecular Oncology, Via Adamello, 16-20139, Milan, Italy. Tel.: 39-02-574303-234. Fax: 39-02574303-244. email: dejana{at}ifom-firc.it

Using the Cre/loxP system we conditionally inactivated ß-catenin in endothelial cells. We found that early phases of vasculogenesis and angiogenesis were not affected in mutant embryos; however, vascular patterning in the head, vitelline, umbilical vessels, and the placenta was altered. In addition, in many regions, the vascular lumen was irregular with the formation of lacunae at bifurcations, vessels were frequently hemorrhagic, and fluid extravasation in the pericardial cavity was observed. Cultured ß-catenin -/- endothelial cells showed a different organization of intercellular junctions with a decrease in {alpha}-catenin in favor of desmoplakin and marked changes in actin cytoskeleton. These changes paralleled a decrease in cell–cell adhesion strength and an increase in paracellular permeability. We conclude that in vivo, the absence of ß-catenin significantly reduces the capacity of endothelial cells to maintain intercellular contacts. This may become more marked when the vessels are exposed to high or turbulent flow, such as at bifurcations or in the beating heart, leading to fluid leakage or hemorrhages.

Key Words: desmoplakin; adherens junctions; angiogenesis; vasculogenesis; vascular permeability

The online version of this article includes supplemental material.

Abbreviation used in this paper: E, embryonic day.


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