Development of the kidneys and urinary tract. (A) The bilateral nephric ducts (NDs; alternatively mesonephric ducts or Wolffian ducts) and the nephric cords (NCs) are the precursor structures of the adult urinary system. Both originate from the embryonic intermediate mesoderm. The cells of the ND undergo an early mesenchymal to epithelial transition and assemble into epithelial tube–like structures. The associated NC retains characteristics of mesenchymal tissue.16,62 (B) As the embryo develops, the ND elongates caudally. At approximately E9.5, the most caudal portion of the ND fuses with the cloacal epithelium (Cl). The cloaca is the embryonic precursor of the bladder, and it is derived from cloacal endoderm.16,66 (C) The NC reorganizes and forms a morphologically distinct domain: the MM. Renal morphogenesis is initiated and maintained by reciprocal interactions between the epithelial ND and the MM. In mice, at embryonic day approximately E10–E10.5, signals from the MM induce the formation of a circumscribed, broad swelling of the ND at the level of the MM.15,16 (D) At E10.5 in mice and around the fifth week of human gestation, the UB emerges from the swollen portion of the ND and grows dorsally toward the MM.4,15,16,74 The caudal part of the ND, which is located between the UB and the insertion into the Cl, is referred to as the common nephric duct (CND). (E) Stimulated by MM-derived signals, the UB begins to branch repeatedly (branching morphogenesis) at approximately E11.5. Through continuous reciprocal induction, the MM is important for promoting and maintaining branching events of the UB. The UB branching continues for approximately 9–13 cycles (mice) and then slows down after approximately E15.5. Via branching morphogenesis, the UB gives rise to the renal collecting system consisting of collecting ducts and renal pelvis as well as the ureter. Reciprocally, signals from the UB also support development of MM cells. The MM that is in closest proximity to the UB tips condenses and forms the so-called cap mesenchyme (CM). Stimulated by signals from the UB, the CM undergoes a mesenchymal to epithelial transition. The epithelial cell population subsequently gives rise to structures of the nephron (glomerulus, the proximal tubule, and the distal tubule). Modified from refs. 16 and 62, with permission.