The initial phase of embryonic kidney development is the interaction between 2 tissues that are derived from the intermediate mesoderm: the metanephrogenic mesenchyme and the mesonephric duct. Kidney development proceeds in 3 successive steps: the pronephros, mesonephros, and adult metanephros. Each of these steps involves mesenchymal-to-epithelial transformation of cells that are derived from the intermediate mesoderm. Among the genes expressed in the mesenchyme that are important in early kidney development are Six1, Six2, Sall1, Pax2, Eya1, Foxc1, Wt1, and Hox11, which encode transcription factors, and Gdf11 and Gdnf, which encode transforming growth factors. A variety of renal abnormalities occur with mutations of these genes. Some of these genes also are involved in the formation of other organs, such as eye and muscle.1
The pronephric duct arises from the intermediate mesoderm early during embryogenesis. This soon becomes the mesonephric, or Wolffian, duct. The metanephrogenic mesenchyme induces the formation of an epithelial branch from each of the paired mesonephric ducts; these branches are the ureteric buds (metanephric diverticula). The ureteric bud emerges from the mesonephric duct and enters the metanephrogenic mesenchyme where it branches and induces the mesenchyme to condense and differentiate into nephrons. Therefore, renal development involves reciprocal interactions between 2 intermediate mesodermal tissues. The ureteric bud fails to branch and elongate in the absence of metanephrogenic mesenchyme; likewise, the mesenchymal tissue undergoes apoptosis in the absence of the ureteric bud. Failure of development of, or early degeneration of, the ureteric bud leads to renal agenesis.
Diffusible signaling molecules produced by the mesenchyme, such as Gdnf (glial-cell-line-derived neurotrophic factor), stimulate budding and elongation of the mesonephric ducts. As the embryonic ureter grows into metanephric blastema, it undergoes a series of dichotomous divisions that eventually form the infundibula, calyces, and collecting ducts of the kidney. The size and functional capacity of the kidney are ultimately determined by the complexity of ureteric bud branching and the number of individual nephrons that have been induced by the time the pool of metanephric stem cells has been consumed and nephrogenesis terminates. Duplication anomalies of the urinary tract result from early division of the ureteric bud. The extent of the duplication relates to the developmental stage at which division of the diverticulum occurred.
The segment of the mesonephric duct that extends from the site of origin of the developing ureter to the primitive cloaca is termed the common excretory duct. The common excretory duct incorporates into the bladder base and proximal urethra. By the end of the sixth gestational week, the ureter and the mesonephric duct have separate openings into the urogenital sinus. As the common excretory duct is absorbed into the urogenital sinus, the original meatus on the mesonephric duct migrates in a cephalic and lateral direction. As the bladder and urethra develop, the ureteral orifice migrates in a lateral and cephalic direction and the ...