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Molecular cloning and expression of murine vascular endothelial- cadherin
in early stage development of cardiovascular system
G Breier, F Breviario, L Caveda, R Berthier, H Schnurch, U Gotsch, D Vestweber, W Risau and E Dejana
Max-Planck-Institut fur physiologische und klinische Forschung, Bad
Nauheim, Germany.
An early step in the formation of the extraembryonic and intraembryonic
vasculature is endothelial cell differentiation and organization in blood
islands and vascular structures. This involves the expression and function
of specific adhesive molecules at cell-to-cell junctions. Previous work
showed that endothelial cells express a cell-specific cadherin (vascular
endothelial [VE]-cadherin, or 7B4/cadherin-5) that is organized at
cell-to-cell contacts in cultured cells and is able to promote
intercellular adhesion. In this study, we investigated whether VE-cadherin
could be involved in early cardiovascular development in the mouse embryo.
We first cloned and sequenced the mouse VE-cadherin cDNA. At the protein
level, murine VE-cadherin presented 75% identity (90%, considering
conservative amino acid substitutions) with the human homologue.
Transfection of murine VE-cadherin cDNA in L cells induced Ca(++)-dependent
cell-to-cell aggregation and reduced cell detachment from monolayers. In
situ hybridization of adult tissues showed that the murine molecule is
specifically expressed by endothelial cells. In mouse embryos, VE-cadherin
transcripts were detected at the very earliest stages of vascular
development (E7.5) in mesodermal cells of the yolk sac mesenchyme. At E9.5,
expression of VE-cadherin was restricted to the peripheral cell layer of
blood islands that gives rise to endothelial cells. Hematopoietic cells in
the center of blood islands were not labeled. At later embryonic stages,
VE-cadherin transcripts were detected in vascular structures of all organs
examined, eg, in the ventricle of the heart, the inner cell lining of the
atrium and the dorsal aorta, in intersomitic vessels, and in the
capillaries of the developing brain. A comparison with flk-1 expression
during brain angiogenesis revealed that brain capillaries expressed
relatively low amounts of VE-cadherin. In the adult brain, the level of
VE-cadherin transcript was further reduced. By immunohistochemistry, murine
VE-cadherin protein was detected at cell-to-cell junctions of endothelial
cells. Overall, these data demonstrate that VE-cadherin is an early,
constitutive, and specific marker of endothelial cells. This distinguishes
this molecule from other cadherins and suggests that its expression is
associated with the early assembly of vascular structures.
Volume 87,
Issue 2,
pp. 630-641,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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