Embryonic renal epithelia: Induction, nephrogenesis, and cell differentiation

Embryonic metanephroi, differentiating into the adult kidney, have come to be a generally accepted model system for organogenesis. Nephrogenesis implies a highly controlled series of morphogenetic and differentiation events that starts with reciprocal inductive interactions between two different primordial tissues and leads, in one of two mainstream processes, to the formation of mesenchymal condensations and aggregates. These go through the intricate process of mesenchyme-to-epithelium transition by which epithelial cell polarization is initiated, and they continue to differentiate into the highly specialized epithelial cell populations of the nephron. Each step along the developmental metanephrogenic pathway is initiated and organized by signaling molecules that are locally secreted polypeptides encoded by different gene families and regulated by transcription factors. Nephrogenesis proceeds from the deep to the outer cortex, and it is directed by a second, entirely different developmental process, the ductal branching of the ureteric bud-derived collecting tubule. Both systems, the nephrogenic (mesenchymal) and the ductogenic (urcteric), undergo a repeat series of inductive signaling that serves to organize the architecture and differentiated cell functions in a cascade of developmental gene programs. The aim of this review is to present a coherent picture of principles and mechanisms in embryonic renal epithelia.