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

Cattelino A, Liebner S, Gallini R, Zanetti A, Balconi G, Corsi A, Bianco P, Wolburg H, Moore R, Oreda B, Kemler R, Dejana E - J. Cell Biol. (2003)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: FIRC Institute of Molecular Oncology, 16-20139, Milan, Italy.

ABSTRACT
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.

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Biochemical characterization of the junctional complex. (A) Association of VE-cadherin with α, β-catenins, and plakoglobin. Endothelial cell extracts from control and β-catenin −/− cells were immunoprecipitated with antibodies to VE-cadherin. The immunoprecipitates (IP) and an equal amount of total protein extracts (Total) from the two cell types were immunoblotted (IB) with the antibodies indicated on the left. Note the decrease in the level of both total and VE-cadherin-bound α-catenin. (B) Increase in desmoplakins level in β-catenin −/− and in control cell lysates. Arrowheads indicate the bands corresponding to desmoplakin I (250 kD) and II (220 kD).
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fig8: Biochemical characterization of the junctional complex. (A) Association of VE-cadherin with α, β-catenins, and plakoglobin. Endothelial cell extracts from control and β-catenin −/− cells were immunoprecipitated with antibodies to VE-cadherin. The immunoprecipitates (IP) and an equal amount of total protein extracts (Total) from the two cell types were immunoblotted (IB) with the antibodies indicated on the left. Note the decrease in the level of both total and VE-cadherin-bound α-catenin. (B) Increase in desmoplakins level in β-catenin −/− and in control cell lysates. Arrowheads indicate the bands corresponding to desmoplakin I (250 kD) and II (220 kD).

Mentions: To study whether the morphological and functional defects observed in β-catenin −/− endothelial cells in vivo were independent from their tissue context, we isolated and cultured endothelial cells from mutant and wild-type embryos. β-Catenin −/− endothelial cells presented all endothelial markers analyzed (Fig. 6–8; unpublished data), but cell morphology was significantly different. β-Catenin −/− cells were more elongated as compared with control cells (Fig. 6, C and D), and presented thinner and longer bundles of actin filaments, with sensibly less organized anchorage sites at the periphery of the cell (Fig. 6, E and F).


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

Cattelino A, Liebner S, Gallini R, Zanetti A, Balconi G, Corsi A, Bianco P, Wolburg H, Moore R, Oreda B, Kemler R, Dejana E - J. Cell Biol. (2003)

Biochemical characterization of the junctional complex. (A) Association of VE-cadherin with α, β-catenins, and plakoglobin. Endothelial cell extracts from control and β-catenin −/− cells were immunoprecipitated with antibodies to VE-cadherin. The immunoprecipitates (IP) and an equal amount of total protein extracts (Total) from the two cell types were immunoblotted (IB) with the antibodies indicated on the left. Note the decrease in the level of both total and VE-cadherin-bound α-catenin. (B) Increase in desmoplakins level in β-catenin −/− and in control cell lysates. Arrowheads indicate the bands corresponding to desmoplakin I (250 kD) and II (220 kD).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172846&req=5

fig8: Biochemical characterization of the junctional complex. (A) Association of VE-cadherin with α, β-catenins, and plakoglobin. Endothelial cell extracts from control and β-catenin −/− cells were immunoprecipitated with antibodies to VE-cadherin. The immunoprecipitates (IP) and an equal amount of total protein extracts (Total) from the two cell types were immunoblotted (IB) with the antibodies indicated on the left. Note the decrease in the level of both total and VE-cadherin-bound α-catenin. (B) Increase in desmoplakins level in β-catenin −/− and in control cell lysates. Arrowheads indicate the bands corresponding to desmoplakin I (250 kD) and II (220 kD).
Mentions: To study whether the morphological and functional defects observed in β-catenin −/− endothelial cells in vivo were independent from their tissue context, we isolated and cultured endothelial cells from mutant and wild-type embryos. β-Catenin −/− endothelial cells presented all endothelial markers analyzed (Fig. 6–8; unpublished data), but cell morphology was significantly different. β-Catenin −/− cells were more elongated as compared with control cells (Fig. 6, C and D), and presented thinner and longer bundles of actin filaments, with sensibly less organized anchorage sites at the periphery of the cell (Fig. 6, E and F).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: FIRC Institute of Molecular Oncology, 16-20139, Milan, Italy.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus