Figure 1.

Wilms' tumors typically consist of three cell types that correspond to the progenitor lineages that co-exist in the nephrogenic zone of the developing fetal kidney. (A) Shown is the developmental hierarchy of the various cell types involved in kidney development. (B) A sketch of nephron formation in the cortex of a fetal kidney with representative nephric structures (UB: Ureteric bud, RV: Renal Vesicle, SSB: S-Shaped body). Three cell types co-exist within the nephrogenic zone: (i) The un-induced metanephric mesenchyme: Mesenchymal cells that are loosely associated, have no polarity, are relatively motile, and are surrounded by an extracellular matrix. A subset of these cells are induced to condense around the ureteric tip and become the Cap mesenchyme. (ii) The Cap mesenchyme: Cells in a transient self-renewing progenitor state that in mammals normally exists only during embryonic stages and is depleted after birth. A subset of these cells undergo a Mesenchymal to Epithelial Transition (MET) and, through a series of differentiation events, differentiate to create the various tubular epithelial segments of the nephron. (iii) Early nephric epithelial structures: Epithelial cells that have a well-defined polarity, are connected by tight junctions, and create two-dimensional surfaces and tubules capable of transport (absorption and secretion). Wilms' tumor is a pediatric malignancy thought to arise from faulty kidney differentiation since it contains cell types that resemble the above three populations of the nephrogenic zone: Stromal cells that correspond to the un-induced metanephric mesenchyme, Blastemal cells that correspond to the Cap mesenchyme, and disorganized epithelial structures that correspond to the early nephric epithelium.