MOLECULAR-CLONING AND EXPRESSION OF MURINE VASCULAR ENDOTHELIAL CADHERIN IN EARLY-STAGE DEVELOPMENT OF CARDIOVASCULAR-SYSTEM

An early step in the formation of the extraembryonic and intraembryoni c vasculature is endothelial cell differentiation and organization in blood islands and vascular structures. This involves the expression an d function of specific adhesive molecules at cell-to-cell junctions. P revious work showed that endothelial cells express a cell-specific cad herin (vascular endothelial [VE]-cadherin, or 7B4/cadherin-5) that is organized at cell-to-cell contacts in cultured cells and is able to pr omote intercellular adhesion. In this study, we investigated whether V E-cadherin could be involved in early cardiovascular development in th e mouse embryo. We first cloned and sequenced the mouse VE-cadherin cD NA. At the protein level, murine VE-cadherin presented 75% identity (9 0%, 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 fr om monolayers. In situ hybridization of adult tissues showed that the murine molecule is specifically expressed by endothelial cells. In mou se 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 endothel ial cells. Hematopoietic cells in the center of blood islands were not labeled. At later embryonic stages, VE-cadherin transcripts were dete cted in vascular structures of all organs examined, eg, in the ventric le of the heart, the inner cell lining of the atrium and the dorsal ao rta, in intersomitic vessels, and in the capillaries of the developing brain. A comparison with flk-1 expression during brain angiogenesis r evealed 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 w as detected at cell-to-cell junctions of endothelial cells. Overall, t hese 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 w ith the early assembly of vascular structures. (C) 1996 by The America n Society of Hematology.