A URETERAL BUD CELL-LINE INDUCES NEPHROGENESIS IN 2 STEPS BY 2 DISTINCT SIGNALS

Nephrons develop from mesenchymal cells that have contacted the ureter ic bud (UB). To determine whether cell associated or secreted ureteric molecules induce the mesenchyme, we have isolated UB cell lines from mice transgenic for T antigen. These cells express epithelial and uret eric (Dolichos lectin staining, c-ret, c-met without hepatocyte growth factor) specific markers, which identifies them as authentic UB cells . Medium conditioned by our cells rescues mesenchyme from apoptosis wi thout inducing the appearance of epithelial aggregates. The same was f ound by culturing mesenchymes upon the apical surface of a UB monolaye r. In contrast, tubules were induced in mesenchymes contacting trypsin ized pellets of UB cells. As revealed by staining for T antigen and Do lichos lectin or by prelabeling UB cells with -dioctadecyl-3,3,3',3'-t etramethylindocarbocyanine perchlorate (DiI), we found that our cells encapsulated the mesenchyme but did not incorporate in the tubules. Th ese data demonstrate that nephrogenesis is stimulated by two distinct ureteric signals, secreted molecules rescue the mesenchyme from apopto sis, whereas diffusion-limited basolateral molecules trigger mesenchym al/epithelial conversion.