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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL045335-04
Application #
3364341
Study Section
Special Emphasis Panel (SRC (BB))
Project Start
1990-07-01
Project End
1995-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Icos Corporation
Department
Type
DUNS #
City
Bothell
State
WA
Country
United States
Zip Code
98021
Haselton, F R; Heimark, R L (1997) Role of cadherins 5 and 13 in the aortic endothelial barrier. J Cell Physiol 171:243-51
Tanihara, H; Kido, M; Obata, S et al. (1994) Characterization of cadherin-4 and cadherin-5 reveals new aspects of cadherins. J Cell Sci 107 ( Pt 6):1697-704
Coffin, J D; Harrison, J; Schwartz, S et al. (1991) Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo. Dev Biol 148:51-62