INVOLVEMENT OF R-CADHERIN IN THE EARLY-STAGE OF GLOMERULOGENESIS

The earliest commitment to the formation of glomeruli is recognizable in S-shaped bodies. Although cell-cell adhesion seems likely to play a crucial role in this process, how glomerular epithelial cells segrega te from the other parts of the nephron is unknown. In this study, immu nofluorescence microscopy and monoclonal antibodies specific for mouse R-, E-, P- and N-cadherins were used to examine which of these adhesi on molecules are involved in glomerulogenesis of the mouse kidney. Wea k R-cadherin staining was first found in the vesicle stage, becoming r estricted to glomerular visceral epithelial cells (VEC) during the S-s haped body stage. The intensity of this staining became stronger in th e capillary loop stage, whereas parietal epithelial cells (PEC) and tu bular cells did not stain. In the maturing stage, VEC gradually lost t heir staining for R-cadherin. E-cadherin was detected in ureteric buds and the upper limb of S-shaped bodies. From the capillary loop to the maturing stage, anti-E-cadherin stained epithelial cells in all tubul e segments, but no label was seen in VEC or PEG. P-cadherin was also s tained in the ureteric buds and in the upper limb of S-shaped bodies. N-Cadherin was weakly stained in cells at the vesicle stage, but there after staining of N-cadherin was not detected at any stage of glomerul ar formation. Immunoelectron microscopy of differentiating VEC was per formed using antibodies specific to alpha-catenin, which is associated with cadherin. Subsequently, immunogold particles identifying alpha-c atenin were localized on junctions between primary processes of VEC. T hese findings indicate that R-cadherin is uniquely expressed in differ entiating VEC, suggesting an important role in the early stages of glo merulogenesis.