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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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Related in: MedlinePlus

Thinner endocardium and increased number of fenestrations in β-catenin– embryos. In electron micrographs, the endocardial lining of the heart appear continuously thinner in the  embryos compared with control littermates (compare A with B), whereas the myocardium is equally organized (not depicted). Ultrathin sections of yolk sac vessels of control and mutant embryos show similar features as the heart endocardium, with thinner endothelial walls and less organized junctions in β-catenin–deficient embryos. In the latter, the inter-endothelial junctions show a reduced junctional overlapping (see arrows), as compared with controls (C and D; asterisks point to fenestrations). Furthermore, a higher incidence of fenestrations (asterisks) in the yolk sac vasculature of  embryos can be observed (compare D, E, and F), which are quantified as number of fenestrae per length unit of endothelial wall (G; 10 pictures counted for each genotype).
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fig5: Thinner endocardium and increased number of fenestrations in β-catenin– embryos. In electron micrographs, the endocardial lining of the heart appear continuously thinner in the embryos compared with control littermates (compare A with B), whereas the myocardium is equally organized (not depicted). Ultrathin sections of yolk sac vessels of control and mutant embryos show similar features as the heart endocardium, with thinner endothelial walls and less organized junctions in β-catenin–deficient embryos. In the latter, the inter-endothelial junctions show a reduced junctional overlapping (see arrows), as compared with controls (C and D; asterisks point to fenestrations). Furthermore, a higher incidence of fenestrations (asterisks) in the yolk sac vasculature of embryos can be observed (compare D, E, and F), which are quantified as number of fenestrae per length unit of endothelial wall (G; 10 pictures counted for each genotype).

Mentions: As shown in Fig. 5, in mutant embryos endocardial and vascular endothelial cells were more elongated than control vessels, resulting in a continuously thinner endothelial layer. The absolute minimum thickness of the endothelium instead was not altered (Fig. 5, A and B). Junctional overlapping typical of endothelial cells was impaired and consistently reduced in essentially all the specimens considered (Fig. 5, C and D).


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)

Thinner endocardium and increased number of fenestrations in β-catenin– embryos. In electron micrographs, the endocardial lining of the heart appear continuously thinner in the  embryos compared with control littermates (compare A with B), whereas the myocardium is equally organized (not depicted). Ultrathin sections of yolk sac vessels of control and mutant embryos show similar features as the heart endocardium, with thinner endothelial walls and less organized junctions in β-catenin–deficient embryos. In the latter, the inter-endothelial junctions show a reduced junctional overlapping (see arrows), as compared with controls (C and D; asterisks point to fenestrations). Furthermore, a higher incidence of fenestrations (asterisks) in the yolk sac vasculature of  embryos can be observed (compare D, E, and F), which are quantified as number of fenestrae per length unit of endothelial wall (G; 10 pictures counted for each genotype).
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Thinner endocardium and increased number of fenestrations in β-catenin– embryos. In electron micrographs, the endocardial lining of the heart appear continuously thinner in the embryos compared with control littermates (compare A with B), whereas the myocardium is equally organized (not depicted). Ultrathin sections of yolk sac vessels of control and mutant embryos show similar features as the heart endocardium, with thinner endothelial walls and less organized junctions in β-catenin–deficient embryos. In the latter, the inter-endothelial junctions show a reduced junctional overlapping (see arrows), as compared with controls (C and D; asterisks point to fenestrations). Furthermore, a higher incidence of fenestrations (asterisks) in the yolk sac vasculature of embryos can be observed (compare D, E, and F), which are quantified as number of fenestrae per length unit of endothelial wall (G; 10 pictures counted for each genotype).
Mentions: As shown in Fig. 5, in mutant embryos endocardial and vascular endothelial cells were more elongated than control vessels, resulting in a continuously thinner endothelial layer. The absolute minimum thickness of the endothelium instead was not altered (Fig. 5, A and B). Junctional overlapping typical of endothelial cells was impaired and consistently reduced in essentially all the specimens considered (Fig. 5, C and D).

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