The Ureteric Bud: Tissue-Culture Approaches to Branching Morphogenesis and Inductive Signaling

As demonstrated in the development of many parenchymal tissues, the metanephros is the product of an epithelial-mesenchymal interaction involving the proliferation, invasion, and branching morphogenesis of an epithelium into a juxtaposed stromal component that creates an appropriate growth environment for the epithelium and helps determine its structural patterning (1 ). However, unlike the majority of such tissues, metanephric development depends upon an epithelium and mesenchyme that both originate from mesoderm, and a characteristic mesenchymal-epithelial conversion that provides the hallmark event of this process. The metanephros itself is derived from reciprocal interactions between an epithelial outgrowth of the mesonephric/Wolffian duct—i.e., the ureteric bud, and the surrounding metanephric mesenchyme, which comprises the caudal aspect of the nephrogenic cord/urogenital tract. The ureteric bud regulates morphogenesis of the mesenchyme both directly through elaboration of inductive factors that determine specification of the mesenchymal component and indirectly through the production of a defined number of branch termini, each of which induces a single nephron. As the progenitor population for the collecting duct, it provides the stimulus in the form of soluble patterning molecules and extracellular matrix (ECM) components for induction, differentiation, and recruitment of cells from the metanephric mesenchyme, generating interstitial stroma as well as the podocytes of the glomeruli and the epithelia of the proximal/distal tubules and the loop of Henle.