CELL-ADHESION RECEPTORS AND EARLY MAMMALIAN HEART DEVELOPMENT - AN OVERVIEW

Cardiovascular development is the end result of a complex genetic prog ram subject to regulation by signals transmitted between a cell and it s extracellular environment. As cells encounter new extracellular matr ices or establish new cell-cell interactions, new genes must be activa ted to accommodate the altered developmental situation within which th e cell finds itself This is likely reflected in, a program of adhesion receptor and counter receptor expression on the surface of cells enga ged in the morphogenesis. To understand the molecular basis of develop ment, it is necessary to first determine if such a program exists and then to establish the role of various receptors and counter receptors in the particular morphogenetic process under investigation. To this e nd, we have initiated an investigation into expression of specific adh esion receptors during cardiovascular development in the mouse. Here, we demonstrate that platelet endothelial cell adhesion molecule (PECAM )-1 is an excellent marker for following vascular formation in the mam malian embryo. It is expressed during development in several alternati vely spliced forms involving the cytoplasmic domain of the molecule. T hese forms differ in their ligand binding properties. Thus, a change i n the cytoplasmic domain affects the folding of the molecule in such a way as to structurally alter the extracellular domain. Further, sever al receptors including the laminin receptor, the fibronectin receptor and a hyaluronic acid receptor, display specific expression patterns d uring heart development. These include differential expression in the endocardium and myocardium, down regulation during endocardial cushion formation and cessation of expression in particular regions of the he art upon maturation. Interference with the function of one of these re ceptors (the fibronectin receptor) results in aberrant heart formation . These observations strongly support the concept that morphogenesis r equires specific cell adhesion molecules that are expressed in precise ly choreographed programs.