PLATELET ENDOTHELIAL-CELL ADHESION MOLECULE-1 (PECAM-1 CD31) - ALTERNATIVELY SPLICED, FUNCTIONALLY DISTINCT ISOFORMS EXPRESSED DURING MAMMALIAN CARDIOVASCULAR DEVELOPMENT

The establishment of the cardiovascular system represents an early, cr itical event essential for normal embryonic development. An important component of vascular ontogeny is the differentiation and development of the endothelial and endocardial cell populations. This involves, at least in part, the expression and function of specific cell surface r eceptors required to mediate cell-cell and cell-matrix adhesion. Plate let endothelial cell adhesion molecule-1 (PECAM-1, CD31) may well serv e such a function. It is a member of the immunoglobulin superfamily ex pressed by the entire vascular endothelium in the adult. It is capable of mediating adhesion by a heterophilic mechanism requiring glycosami noglycans, as well as by a hemophilic, glycosaminoglycan independent, mechanism. It has been shown to regulate the expression of other adhes ion molecules on naive T cells. This report documents by RT-PCR and im munohistochemical analysis the expression of PECAM-1 during early post implantation mouse embryo development. PECAM-1 was expressed by early endothelial precursors first within the yolk sac and subsequently wit hin the embryo itself. Interestingly, embryonic PECAM-1 was expressed as multiple isoforms in which one or more clusters of polypeptides wer e missing from the cytoplasmic domain. The sequence and location of th e deleted polypeptides corresponded to exons found in the human PECAM- 1 gene. The alternatively spliced isoforms were capable of mediating c ell-cell adhesion when transfected into L-cells. The isoforms differed , however, in their sensitivity to a panel of anti-PECAM-1 monoclonal antibodies. These data suggest that changes in the cytoplasmic domain of PECAM-1 may affect its function during cardiovascular development, and are consistent with our earlier report that systematic truncation of the cytoplasmic domain of human PECAM-1 resulted in changes in its ligand specificity, divalent cation and glycosaminoglycan dependence, as well as its susceptibility to adhesion blocking monoclonal antibodi es. This is the first report of naturally occurring alternatively spli ced forms of PECAM-1 having possible functional implications.