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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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Junctional organization in control and mutant embryos. Cryosections from E10.5 embryos were analyzed for the codistribution of PECAM (A and B) and α-catenin (C and D). PECAM is equally expressed in control (A) and mutant embryos (B), and in some regions it is possible to evidentiate its localization at cell–cell contacts (arrows). In contrast, in mutant embryos α-catenin shows a weaker endothelial staining and colocalization with PECAM at intercellular junctions is rare (compare C and D, arrows). Desmoplakin is detectable in endothelial cells in β-catenin– embryos and colocalizes with PECAM at cell–cell contacts (F and H). In control embryos desmoplakin staining was negative in endothelial cells (E and G). e, endocardium. Bar in H refers to A–H.
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fig9: Junctional organization in control and mutant embryos. Cryosections from E10.5 embryos were analyzed for the codistribution of PECAM (A and B) and α-catenin (C and D). PECAM is equally expressed in control (A) and mutant embryos (B), and in some regions it is possible to evidentiate its localization at cell–cell contacts (arrows). In contrast, in mutant embryos α-catenin shows a weaker endothelial staining and colocalization with PECAM at intercellular junctions is rare (compare C and D, arrows). Desmoplakin is detectable in endothelial cells in β-catenin– embryos and colocalizes with PECAM at cell–cell contacts (F and H). In control embryos desmoplakin staining was negative in endothelial cells (E and G). e, endocardium. Bar in H refers to A–H.

Mentions: The organization of endothelial cell junctions was also studied in vivo by immunostaining of vascular sections of E10.5 embryos. Consistently with the data obtained on cultured cells, we found that α-catenin was barely visible at interendothelial contacts of mutant embryos as compared with controls (Fig. 9, A–D). Desmoplakin was detectable only in the endothelium of mutant mice, but not in controls (Fig. 9, E to H, arrows). VE-cadherin and plakoglobin were correctly expressed in mutant and control mice (Fig. S4, available at http://www.jcb.org/cgi/content/full/jcb.200212157/DC1). Therefore, endothelial immunostaining in vivo supports the observations made on cultured cells.


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)

Junctional organization in control and mutant embryos. Cryosections from E10.5 embryos were analyzed for the codistribution of PECAM (A and B) and α-catenin (C and D). PECAM is equally expressed in control (A) and mutant embryos (B), and in some regions it is possible to evidentiate its localization at cell–cell contacts (arrows). In contrast, in mutant embryos α-catenin shows a weaker endothelial staining and colocalization with PECAM at intercellular junctions is rare (compare C and D, arrows). Desmoplakin is detectable in endothelial cells in β-catenin– embryos and colocalizes with PECAM at cell–cell contacts (F and H). In control embryos desmoplakin staining was negative in endothelial cells (E and G). e, endocardium. Bar in H refers to A–H.
© Copyright Policy
Related In: Results  -  Collection

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

fig9: Junctional organization in control and mutant embryos. Cryosections from E10.5 embryos were analyzed for the codistribution of PECAM (A and B) and α-catenin (C and D). PECAM is equally expressed in control (A) and mutant embryos (B), and in some regions it is possible to evidentiate its localization at cell–cell contacts (arrows). In contrast, in mutant embryos α-catenin shows a weaker endothelial staining and colocalization with PECAM at intercellular junctions is rare (compare C and D, arrows). Desmoplakin is detectable in endothelial cells in β-catenin– embryos and colocalizes with PECAM at cell–cell contacts (F and H). In control embryos desmoplakin staining was negative in endothelial cells (E and G). e, endocardium. Bar in H refers to A–H.
Mentions: The organization of endothelial cell junctions was also studied in vivo by immunostaining of vascular sections of E10.5 embryos. Consistently with the data obtained on cultured cells, we found that α-catenin was barely visible at interendothelial contacts of mutant embryos as compared with controls (Fig. 9, A–D). Desmoplakin was detectable only in the endothelium of mutant mice, but not in controls (Fig. 9, E to H, arrows). VE-cadherin and plakoglobin were correctly expressed in mutant and control mice (Fig. S4, available at http://www.jcb.org/cgi/content/full/jcb.200212157/DC1). Therefore, endothelial immunostaining in vivo supports the observations made on cultured cells.

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