Transcriptional control of renal collecting duct development

Abstract

METANEPHRIC KIDNEY DEVELOPMENT is a complex process involving maturational changes and reciprocal signaling between epithelial and mesenchymal tissues. Over the last 15–20 years, the number of reports on kidney development has increased, with the vast majority focused on early events such as interactions between the ureteric bud and metanephric mesenchyme, ureteric bud branching morphogenesis, and induction of glomeruli and nephrons (1, 14). Although these events are clearly important, another critical process is the maturation and differentiation of distal portions of the ureteric bud into specialized collecting duct epithelia. In fact, failure of the normal maturation of the ureteric bud into collecting ducts is likely one of the causes of renal dysplasia in humans (12). The report by Saifudeen et al. (9) in this issue of American Journal of Physiology-Renal Physiology is another in a series of elegant reports from Dr. Samir El-Dahr’s laboratory that begin to dissect out the molecular control of collecting duct differentiation and maturation. The ureteric bud arises as an outgrowth of the nephric duct at around 5 wk gestation in the human and embryonic day 11 (E11) in the mouse and E12 in the rat (6). Once it makes contact with the surrounding metanephric mesenchyme, it undergoes a series of dichotomous branchings. The terminal tips of the ureteric bud induce the formation of nephrons from the surrounding mesenchyme. Ultimately, the main trunk of the ureteric bud gives rise to the mature ureter, whereas the early branches become the renal pelvis and calices. The distal branches of the ureteric bud fuse with the developing nephrons (from the mesenchyme) and mature into the heterogeneous collecting duct epithelia to generate functional units in the kidney. The genetic control of distal ureteric bud maturation has