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.