DIFFERENTIAL EXPRESSION AND FUNCTION OF CADHERIN-6 DURING RENAL EPITHELIUM DEVELOPMENT

The cadherin gene family encodes calcium-dependent adhesion molecules that promote hemophilic interactions among cells, During embryogenesis , differential expression of cadherins can drive morphogenesis by stim ulating cell aggregation, defining boundaries between groups of cells and promoting cell migration, In this report, the expression patterns of cadherins were examined by immunocytochemistry and in situ hybridiz ation in the embryonic kidney, during the time when mesenchymal cells are phenotypically converted to epithelium and the pattern of the deve loping nephrons is established, At the time of mesenchymal induction, cadherin-11 is expressed in the mesenchyme but not in the ureteric bud epithelium, which expresses E-cadherin, The newly formed epithelium o f the renal vesicle expresses E-cadherin near the ureteric bud tips an d cadherin-6 more distally, suggesting that this primitive epithelium is already patterned with respect to progenitor cell types, In the s-s haped body, the cadherin expression patterns reflect the developmental fate of each region, The proximal tubule progenitors express cadherin -6, the distal tubule cells express E-cadherin, whereas the glomeruli express P-cadherin, Ultimately, cadherin-6 is down-regulated whereas E -cadherin expression remains in most, if not all, of the tubular epith elium. Antibodies generated against the extracellular domain of cadher in-6 inhibit aggregation of induced mesenchyme and the formation of me senchyme-derived epithelium but do not disrupt ureteric bud branching in vitro, These data suggest that cadherin-6 function is required for aggregation of induced mesenchymal cells subsequent conversion to epit helium.