PHENOTYPIC CONVERSIONS IN RENAL DEVELOPMENT

The transporting epithelia of the kidney are derived from an embryonic rudiment containing two distinct cell populations: ureteric bud epith elia and mesenchymal cells of the metanephric blastema. The ureteric b ud is a caudal outgrowth of the Wolffian Duct and gives rise to the re nal collecting system by branching morphogenesis. The metanephric blas tema gives rise to diverse cells of the nephron after receiving an ind uctive stimulus. It has been proposed that mesenchymal progenitors of the metanephric blastema derive directly from intermediate mesoderm, a lthough this hypothesis has never been tested directly. Utilizing dire ct lineage analysis techniques we demonstrate, in an organ culture sys tem, that mesenchymal nephron progenitors are immediate descendants of ureteric bud epithelia. Ureteric bud epithelia can give rise to mesen chymal nephron progenitors that populate the metanephric blastema by u ndergoing an epithelial-to-mesenchymal transition followed by delamina tion. If this process occurs in vivo, renal morphogenesis can be chara cterized by two phenotypic conversions: an epithelial-to -mesenchymal transition leading to the generation of mesenchymal-nephron progenitor s, followed by a mesenchymalto-epithelial transition leading to the ge neration of diverse nephron epithelial cell types. We have immortalize d an embryonic renal mesenchymal cell line and demonstrate that the cl onal cell line, RSTEM-1, undergoes phenotypic conversions in vitro, pr oviding a suitable model to study the regulation of the epithelial phe notype.