Budding angiogenesis and neovascularization have been studied in detail for several years and as a result, we know quite a bit about the biology and biochemistry of angiogenesis. In contrast, nothing is known concerning the process of formation of the initial vascular system in the early embryo. This is because until now, probes have not been available for identifying the earliest embryonic endothelial cells and for following their organization into the vascular tree which subsequently serves as the source of cells for the later process of budding angiogenesis and tissue vascularization. We have developed monoclonal antibodies which react with these early endothelial cells as they first arise from the mesoderm of quail blastodiscs. Using these antibodies in conjunction with monoclonal antibodies specific for individual extracellular matrix molecules (ECM) we propose to first describe the formation of the initial vascular tree and changes which occur in the ECM during this process. Second, we will examine the interaction between the developing vascular endothelium and individual ECM molecules both in cultured embryos and in cultures of isolated endothelial cells. Third, we will identify the receptors in the developing endothelium responsible for adhesion to the ECM. Fourth, we will study the ability of developing endothelial cells to respond to known chemotatic or angiogenic substances as well as attempt to discover whether or not such factors play a role in the establishment of the initial embryonic vasculature. Upon completion of the work proposed here, we will have defined the process of early vascular development, determined the role the ECM plays in this process and gained some insight into the origin and organization of the earliest presumptive vascular endothelial cells into the first vessels of the developing embryo.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL039023-05
Application #
3355555
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Kwee, L; Baldwin, H S; Shen, H M et al. (1995) Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. Development 121:489-503
Yan, H C; Baldwin, H S; Sun, J et al. (1995) Alternative splicing of a specific cytoplasmic exon alters the binding characteristics of murine platelet/endothelial cell adhesion molecule-1 (PECAM-1). J Biol Chem 270:23672-80
Baldwin, H S; Shen, H M; Yan, H C et al. (1994) Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development. Development 120:2539-53
DeLisser, H M; Chilkotowsky, J; Yan, H C et al. (1994) Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) result in changes in ligand binding properties. J Cell Biol 124:195-203
Edelman, J M; Chan, B M; Uniyal, S et al. (1994) The mouse VLA-2 homologue supports collagen and laminin adhesion but not virus binding. Cell Adhes Commun 2:131-43
Mette, S A; Pilewski, J; Buck, C A et al. (1993) Distribution of integrin cell adhesion receptors on normal bronchial epithelial cells and lung cancer cells in vitro and in vivo. Am J Respir Cell Mol Biol 8:562-72
DeLisser, H M; Yan, H C; Newman, P J et al. (1993) Platelet/endothelial cell adhesion molecule-1 (CD31)-mediated cellular aggregation involves cell surface glycosaminoglycans. J Biol Chem 268:16037-46
Piali, L; Albelda, S M; Baldwin, H S et al. (1993) Murine platelet endothelial cell adhesion molecule (PECAM-1)/CD31 modulates beta 2 integrins on lymphokine-activated killer cells. Eur J Immunol 23:2464-71
Klein, S; Giancotti, F G; Presta, M et al. (1993) Basic fibroblast growth factor modulates integrin expression in microvascular endothelial cells. Mol Biol Cell 4:973-82
Buck, C A; Baldwin, H S; DeLisser, H et al. (1993) Cell adhesion receptors and early mammalian heart development: an overview. C R Acad Sci III 316:838-59

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