Preferential cell associations arise in large part from differences in cellular adhesive properties with the result that regulation of those properties can in principle guide the organization of cells into anatomically """"""""correct"""""""" structures. By corollary, errors in such regulation probably underlie at least in part the metastatic behavior of malignant cells and the morphogenetic aberrations leading to specific birth defects. A detailed knowledge of the molecular mechanisms generating cellular adhesive properties is thus essential to our understanding of diverse morphogenetic phenomena. In that context, this work proposes to investigate the role of the dual adhesion mechanisms described earlier in organizing the chick visual system. Recently generated monoclonals antibodies inhibitory of retinal Ca++ dependent (CD) aggregation will be used to identify and isolate components of the retinal CD adhesion mechanism. The molecules so identified will be characterized by molecular weight, pI and carbohydrate composition and their relationship to already identified CD molecules (ie., CaT, ligatin) determined. In exploring the regulatory potential of this mechanism, efforts will be made to elucidate the molecular basis for Ca++ dependent activity (cell-cell bonding) and protection from proteolysis. To complement this line of investigation experiments will also be performed to determine if molecules other than N-CAM contribute to retinal Ca++ independent (CI) adhesion. An array of monoclonal and monospecific polyclonal antibodies against CD and CI (non-CAM) adhesion molecules will then be used to 1) visualize the distribution of those molecules in the retina and other embryonic chick tissues, 2) to explore the structural relationship between functionally similar adhesion molecules from different tissues, 3) to investigate the role of CI and CD molecules in generating known adhesive gradients across the retina and tectum, and finally 4) to test the role of those in directing retino-tectal mapping. Cellular adhesiveness (rate, selectivity) will be tested using cell monolayer and aggregometer assays. Other work will be performed using various electrophoretic techniques, protein blotting, peptide mapping, affinity chromatography, immunochemistry and fluorescence microscopy.
| Thomas, W A; Schaefer, A W; Treadway Jr, R M (1990) Galactosyl transferase-dependence of neurite outgrowth on substratum-bound laminin. Development 110:1101-14 |
| Thomas, W A; Yancey, J (1988) Can retinal adhesion mechanisms determine cell-sorting patterns: a test of the differential adhesion hypothesis. Development 103:37-48 |
