Renal stem cells and the lineage of the nephron.

Abstract

Regulation of the volume and composition of body fluids in multicellular organisms is mediated by at least 14 distinct transporting renal cell types. These heterogeneous epithelial cell types are not randomly distributed throughout the kidney, but are organized into identical functional units called uriniferous tubules. Each uriniferous tubule contains all renal epithelial cell types, and for the purposes of this review, the segmental organization of the uriniferous tubule will be described according to anatomical conventions (1). That is, the uriniferous tubule is composed of a long convoluted portion, the nephron (glomerulus through distal convoluted tubule), and the collecting tubule system (Figure l a). The complex architecture of the uriniferous tubule is a requisite for normal renal function. Renal morphogenesis must be tightly regulated during development so that the correct renal cell type comes to reside in its appropriate nephron segment, and each segment of all uriniferous tubules align to form the gross anatomical compartments of the organ. The metanephric kidney develops from an embryonic rudiment composed of two tissue layers, the epithelial ureteric bud and the mesenchyme of the metanephric blastema (Figure Ib). These two embryonic primordia give rise to separate parts of the uriniferous tubule. The ureteric bud, a caudal outgrowth of the Wolffian duct, forms the collecting tubule system by undergoing branching morphogenesis (32). Grobstein, in his classic exper-