The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility.
Using the Cre/loxP system we conditionally inactivated beta-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 beta-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 beta-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.
Cattelino
Anna
A
FIRC Institute of Molecular Oncology, 16-20139, Milan, Italy.
Liebner
Stefan
S
Gallini
Radiosa
R
Zanetti
Adriana
A
Balconi
Giovanna
G
Corsi
Alessandro
A
Bianco
Paolo
P
Wolburg
Hartwig
H
Moore
Robert
R
Oreda
Boussadia
B
Kemler
Rolf
R
Dejana
Elisabetta
E
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000002:abnormalities* / Q000473:pathology / Q000648:ultrastructure; D002199:Capillary Permeability / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D002463:Cell Membrane Permeability / Q000235:genetics; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D051180:Desmoplakins; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D004699:Endocardium / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000002:abnormalities* / Q000473:pathology / Q000648:ultrastructure; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020868:Gene Silencing / Q000502:physiology; D005804:Genes, Lethal / Q000235:genetics; D007365:Intercellular Junctions / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018919:Neovascularization, Physiologic / Q000235:genetics*; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D051176:beta Catenin
D000199:Actins; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495295:Dsp protein, mouse; D015534:Trans-Activators; D051176:beta Catenin