ROLE OF V-CADHERIN IN VASCULAR MORPHOGENESIS

This study is designed to study the role of cell-cell adhesion in the
formation of the vascular pattern. We have identified a new Ca2+-dependent
cell adhesion molecule in endothelium (V-cadherin). During the
establishment of the axis of the mouse embryo angioblasts segregate from
the mesoderm forming the lumen of the vessel. We will develop a monoclonal
antibody to identify the cells with the aim of isolating them in cell
culture. This marker will help us to see if angioblasts contain V-cadherin
or whether it is only expressed in endothelium. Regulation of expression of
V-cadherin occurs with stimulation of growth by growth factor and
extracellular matrix. We will follow both proliferation and V-cadherin
expression during the temporal and spatial organization of the aorta in the
mouse embryo. As the endothelium becomes defined, there is an expression of
von Willebrand factor in the major vessels, but not in many capillaries. We
will use in situ techniques to see if both of these cells express mRNA for
vWf. Finally we want to use neutralizing antibodies to see what role
V-cadherin plays in blood vessel formation. The process of vasculogenesis of the dorsal aortas is characterized by the
in situ differentiation of angioblasts and the maturation of these cells
into the two cords of endothelium. We have focused on the role of the
Ca2+-dependent cell adhesion in the localization of this process.