Pronephros, Mesonephros, and Metanephros

Here we will learn about the development of the urinary system starting in week 4, with a focus on the formation of the pronephros, mesonephros, and metanephros. During approximately weeks 4 and 5, three sets of excretory structures emerge; two regress, and the third eventually matures to the adult form. These systems develop and regress from cranial to caudal, and overlap chronologically. The pronephros is the first system to emerge, early in week 4. We show the embryo, and show the yolk stalk (aka vitelline duct), hindgut, cloaca, and allantois, and we indicate the location of the intermediate mesoderm along the posterior abdominal cavity; both the urinary and genital systems arise from a common ridge in this mesoderm. The pronephric ducts arise in the cervical segments as rods of condensed mesoderm, which then undergo epithelialization. Five to seven pronephric vesicles (aka, nephrotomes) form simultaneously in the mesoderm; these small, hollow balls of epithelia are nonfunctional, and completely regress within a week of emerging. The pronephros is a vestigial structure in humans, but is responsible for excretion in early vertebrates (i.e., lampreys). As the pronephros regresses during week 4, the mesonephros emerges in the thoracic region. Early stage: we show the lower portion of the embryo including the hindgut and allantois. In the intermediate mesoderm, we show that the pronephric ducts continue to growth caudally as their cranial ends degenerate. Their elongation is driven by mesenchymal-epithelial cell conversions taking place at their caudal tips; notice that they extend from the thoracic region to the middle lumbar region. Mesonephric tubules develop in the mesoderm, also in cranial to caudal direction. The tubules form connections to the ducts, which are now called the mesonephric (aka, Wolffian) ducts. Twenty to forty mesonephric tubules will form, but, because older buds regress as new buds form, there are never this many present at once. Later stage: we re-draw the embryo and show two important developments. The allantois and yolk stalk are now combined within the umbilical cord, and the expanding urogenital sinus is separate from the hindgut. In the intermediate mesoderm, we indicate that the mesonephric ducts elongate and empty into the urogenital sinus. The cranial-most mesonephric buds regress as caudal buds emerge. Eventually, the most of the mesonephros degenerates in the female (remnants can be found as the epoophoron, paraoophoron, and Gartner cyst); in the male, it persists to contribute to the reproductive duct system. Metanephros, aka, the definitive kidney. We show the embryo with the hindgut, urogenital sinus, intermediate mesoderm, and regressing mesonephros. The ureteric bud arises as an outgrowth of the mesonephric duct, near its connection with the urogenital sinus. Signaling between the metanephric mesenchyme and the mesonephric duct/ureteric bud epithelium drives ureteric bud outgrowth; specifically, GNDF, which is produced by the metanephric mesenchyme, binds RET receptors expressed on the ureteric bud. The bud grows towards, and, eventually into, the metanephric mesenchyme (aka, blastema). Upon contact, cellular interactions between the ureteric bud and the metanephric mesoderm drive repeated rounds of bifurcation the ureteric bud and the generation of excretory units (the nephrons) in the mesoderm (these processes are discussed in detail, elsewhere). Nephrogenesis, which we'll discuss in more detail separately, concludes before birth, but the kidney will continue to grow and develop postnatally.