Integration of proliferation and differentiation phenomena during rodent kidney ontogeny

In order to integrate proliferation and differentiation patterns during kidney development, precise ontogenic profiles of several morphometric and biochemical parameters were determined in the mouse. During early nephron formation (before the age of 15 days postnatal), rates of kidney growth and cell proliferation proceed in an independent fashion. DNA synthesis, as measured by 3H-thymidine incorporation, falls rapidly during early metanephrogenesis and is characterized by 3 transitional phases or plateaus. On the other hand, brush border enzyme activities, namely alkaline phosphatase and gamma-glutamyltransferase, increase progressively during this period, although both ontogenic profiles also reveal 3 distinct transitory phases. The plateaus occur synchronously: all are initiated at 16 days of gestation, at birth and at 6 days postnatally. During the final phase of metanephrogenesis (from 15 days onward), kidney and body weights now increase proportionally. In fact, kidney/body (K/B) weight ratios remain remarkably uniform, as defined by the function: K = 12.1 x B.84. Considered together, these results demonstrate that global metanephric development can be separated into early and final stages. The early stage is characterized by complex organo-genetic processes in which proliferation and differentiation profiles seem to be reciprocally related. The late phase, on the other hand, is associated with the interruption of nephronic induction and a constant relationship between organ weight and body weight. Establishing precise developmental profiles of nephronic proliferation and differentiation should provide for a better understanding of metanephrogenesis regulation.