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Metanephros Development
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Metanephros Development

metanephros
The definitive kidney; it comprises a collecting system and excretory units.
  • Recall that the definitive kidney arises from the ureteric bud, which gives rise to the collecting system, and the metanephric mesoderm, which gives rise to the excretory units, the nephrons.
Origins & Interactions of the ureteric bud and metanephric mesoderm
  • The ureteric bud arises as an outgrowth of the mesonephric ducts
— It grows towards, and ultimately into, the metanephric mesoderm (which is also of intermediate mesoderm origin).
  • When the ureteric bud meets the metanephric mesoderm, cellular interactions induce a series of bifurcations.
— Hilum is area where the ureteric bud enters the metanephric mesoderm; later, the renal vein and artery will also pass through here.
  • First bifurcation creates renal pelvis, bud becomes ureter. In the adult form, the ureter carries urine from the kidney to the bladder, for storage.
  • Mesenchymal caps from at the tips of each new bud
— Cellular interactions between the buds and the caps drive each round of bifurcation.
Though researchers are still identifying the precise signaling pathways behind the mechanism, we know that without the mesenchymal caps, branching does not occur.
Furthermore, Wnt9B, which is expressed in the tips of the ureteric buds, is important in the branching response.
  • After 4 generations, (rounds) of bifurcations, the ureteric buds coalesce to form 2-4 major calyces.
  • After the next 4 generations of bifurcations, ureteric buds coalesce again, forming the minor calyces.
Continued bifurcation ultimately gives rise to millions of collecting ducts, which drain the excretory units. In the adult form, urine travels through the collecting ducts, into the minor, then major, calyces, and through the renal pelvis to the ureter.
Formation of the excretory units, aka, the nephrons
Mechanisms driving the emergence of the ureteric bud from the meseonephric duct and the subsequent branching of the ureteric bud are similar.
  • The excretory units arise from metaneprhic mesoderm
  • Nephrogenesis continues post-natally
Four key stages of their development: 1. Renal vesicle formation
  • The ureteric bud expresses FGF, LIP, and Wnt9B, which induce mesenchymal cap release of Wnt4.
  • Wnt4 is a sequential inductive signal that is promotes epithelialization of nearby condensed mesenchyme, and, ultimately, renal vesicle formation.
2. Body formation
  • The renal vesicle grows, transitioning first to a "comma-shaped" vesicle, (aka, body) then, to an "S-Shaped" vesicle.
— The vesicles are polarized with respect to gene expression; in other words, specific genes are expressed in specific domains. 3. Vascularization: endothelial precursors migrate to the proximal ends of the vesicles. 4. Functional form — Collecting ducts connected to nephrons. — At the proximal end of the nephron is the glomerulus, which is a specialized "tuft" of capillaries that arose from the endothelial precursors in our previous diagram. — Bowman's capsule (aka, glomerular capsule ) surrounds the glomerulus.
Urine formation
  • In the functioning kidney, blood flows through millions of glomeruli, where water, wastes, and other solutes are filtered.
  • Fetal urine is excreted to the amniotic cavity, which helps maintain the amniotic fluid volume.
  • Postnatally, the urine content is fine-tuned to maintain acid-base and body water homeostasis as it passes through the nephron; during pregnancy, the placenta performs these functions.

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