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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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Vascular defects in the placenta and head of endothelial β-catenin– embryos. Whole-mount immunohistochemistry for anti-PECAM antibody in E10.5 embryos (A and B). In the head, mutant embryos (B and D) compared with controls (A and C) show a less organized vascular network with vessels of irregular diameter and shape. In mutants, blind ending vessels (B, arrowhead) and lacunae-like bifurcations (D, arrowhead) can be often observed. PECAM and nuclear fast red staining in two serial transverse sections, separated by 60 μm, of E10.5 mutant head (E and F). The arrows point to the diameter of the internal carotid artery, which is significantly different in the two sections. Placenta histology of control (G and I) and mutant E10.5 embryos (H and J) shows that, although the maternal decidua (md), the chorionic plate (cp), and the trophoblast giant cells (tgc) are comparable, the labyrinthine layer (lbr) is reduced in mutants. I and J represent higher magnifications of the zones indicated by the asterisks in G and H, respectively. Embryonic blood vessels (arrows), are substantially more abundant in the labyrinthine zone of the control (I), than in the mutant (J).
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fig3: Vascular defects in the placenta and head of endothelial β-catenin– embryos. Whole-mount immunohistochemistry for anti-PECAM antibody in E10.5 embryos (A and B). In the head, mutant embryos (B and D) compared with controls (A and C) show a less organized vascular network with vessels of irregular diameter and shape. In mutants, blind ending vessels (B, arrowhead) and lacunae-like bifurcations (D, arrowhead) can be often observed. PECAM and nuclear fast red staining in two serial transverse sections, separated by 60 μm, of E10.5 mutant head (E and F). The arrows point to the diameter of the internal carotid artery, which is significantly different in the two sections. Placenta histology of control (G and I) and mutant E10.5 embryos (H and J) shows that, although the maternal decidua (md), the chorionic plate (cp), and the trophoblast giant cells (tgc) are comparable, the labyrinthine layer (lbr) is reduced in mutants. I and J represent higher magnifications of the zones indicated by the asterisks in G and H, respectively. Embryonic blood vessels (arrows), are substantially more abundant in the labyrinthine zone of the control (I), than in the mutant (J).

Mentions: In the embryo proper, the vascular pattern in the head was defective (Fig. 3, A–D). Whole-mount staining with anti-PECAM antibodies showed an altered development of blood vessels in the primitive neural plexus. Namely, blind ending vessels and the formation of lacunae-like bifurcations were observed in the mutants (Fig. 3, B and D, arrowheads). Furthermore, cephalic vessels in the mutants showed an inconstant diameter and often formed acute turns and branching as compared with the control (Fig. 3, C and D, arrowhead). Transverse histological sections of the head confirmed the irregularity of vessel diameter, as indicated, by the different size of the internal carotid artery, shown in two sequential sections of the mutant embryos (Fig. 3, E and F, arrows).


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)

Vascular defects in the placenta and head of endothelial β-catenin– embryos. Whole-mount immunohistochemistry for anti-PECAM antibody in E10.5 embryos (A and B). In the head, mutant embryos (B and D) compared with controls (A and C) show a less organized vascular network with vessels of irregular diameter and shape. In mutants, blind ending vessels (B, arrowhead) and lacunae-like bifurcations (D, arrowhead) can be often observed. PECAM and nuclear fast red staining in two serial transverse sections, separated by 60 μm, of E10.5 mutant head (E and F). The arrows point to the diameter of the internal carotid artery, which is significantly different in the two sections. Placenta histology of control (G and I) and mutant E10.5 embryos (H and J) shows that, although the maternal decidua (md), the chorionic plate (cp), and the trophoblast giant cells (tgc) are comparable, the labyrinthine layer (lbr) is reduced in mutants. I and J represent higher magnifications of the zones indicated by the asterisks in G and H, respectively. Embryonic blood vessels (arrows), are substantially more abundant in the labyrinthine zone of the control (I), than in the mutant (J).
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Vascular defects in the placenta and head of endothelial β-catenin– embryos. Whole-mount immunohistochemistry for anti-PECAM antibody in E10.5 embryos (A and B). In the head, mutant embryos (B and D) compared with controls (A and C) show a less organized vascular network with vessels of irregular diameter and shape. In mutants, blind ending vessels (B, arrowhead) and lacunae-like bifurcations (D, arrowhead) can be often observed. PECAM and nuclear fast red staining in two serial transverse sections, separated by 60 μm, of E10.5 mutant head (E and F). The arrows point to the diameter of the internal carotid artery, which is significantly different in the two sections. Placenta histology of control (G and I) and mutant E10.5 embryos (H and J) shows that, although the maternal decidua (md), the chorionic plate (cp), and the trophoblast giant cells (tgc) are comparable, the labyrinthine layer (lbr) is reduced in mutants. I and J represent higher magnifications of the zones indicated by the asterisks in G and H, respectively. Embryonic blood vessels (arrows), are substantially more abundant in the labyrinthine zone of the control (I), than in the mutant (J).
Mentions: In the embryo proper, the vascular pattern in the head was defective (Fig. 3, A–D). Whole-mount staining with anti-PECAM antibodies showed an altered development of blood vessels in the primitive neural plexus. Namely, blind ending vessels and the formation of lacunae-like bifurcations were observed in the mutants (Fig. 3, B and D, arrowheads). Furthermore, cephalic vessels in the mutants showed an inconstant diameter and often formed acute turns and branching as compared with the control (Fig. 3, C and D, arrowhead). Transverse histological sections of the head confirmed the irregularity of vessel diameter, as indicated, by the different size of the internal carotid artery, shown in two sequential sections of the mutant embryos (Fig. 3, E and F, arrows).

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