Joint study on cell adhesion molecules in development

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In vertebrate embryogenesis, cell adhesion molecules play fundamental roles in development and morphogenesis. We previously reported that cadherin mediated Ca^<2+> dependent cell-cell adhesion system is the only cell adhesion system functional in early frog embryogenesis. Recently, we found that the function of this Ca^<2+> dependent cell-cell adhesion system is completely disrupted by an antihuman blood group B monoclonal antibody. Fab fragments of the antibody or purified blood group B active substances also disrupted Ca^<2+> dependent cell adhesion, and the inhibition of cadherin-mediated cell adhesion is not due to the steric hindrance caused by the antibody. The blood group B active determinant was detected on glycolipids and on glycoproteins. We determined the complete structure of the blood group B active pentaglycosylceramides found in blastula cells. The glycoepitoe was not found on cadherins. The glycoproteins with blood group B epitopes were partially purified in our laboratory. By measuring resonance energy transfer between two molecules, we showed that the human blood group B active determinants colocalize with E-cadherins in tadpoles, and with XB-cadherins in blastulae. Thus, it is highly possible that human blood type B determinant associates with cadherin and is regulating cadherin functions by forming supramolecular complex with them. To analyze the nature of this interaction in embryogenesis, we prepared dominant negative forms of XB-cadherins and made them expressed in early embryogenesis. The morphogenesis and development of the frog embryos were markedly affected by expressing dominant negative cadherins, and the interactions of blood group B active determinant and cadherins were severely disrupted. We are now analyzing the distribution and function of blood group B active determinants in these embryos. Knocking out of the maternal pool of cadherins by antisense oligonucleotides is also being tried by using newly refined technique.