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.

Full-Length Text

Here we will learn about the development of the metanephros, the definitive kidney, which 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.
To begin, let's illustrate the origins of the ureteric bud and metanephric mesoderm.
For embryological context, outline the lower portion of the embryo at approximately week 5;
Show the hindgut, cloaca, urogenital sinus, and, where the allantois and vitelline duct (aka, yolk stalk) travel together, label the umbilical cord.
Then, indicate the intermediate mesoderm.
Within the mesoderm, indicate the mesonephric ducts and tubules; notice that, at this stage, the cranial-most tubules have degenerated. Recall that the caudal ends of the mesonephric ducts are fused with the urogenital sinus.
Now, show that 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).
With this early stage established, let's show how the ureteric bud and metanephric mesoderm interact to form the collecting system, which includes the renal pelvis, calyces, and collecting ducts.
We'll do so in four diagrams.
First, show that when the ureteric bud meets the metanephric mesoderm, cellular interactions induce a series of bifurcations.
Where the ureteric bud enters the metanephric mesoderm, label the renal hilum; later, the renal vein and artery will also pass through here.
Re-draw the metanephric mesoderm (aka, blastema) and show the ureteric bud after two rounds of bifurcations;
Label the renal pelvis, which was created by the first bifurcation of the ureteric bud, and,
Indicate that we can now refer to the bud as the ureter. In the adult form, the ureter carries urine from the kidney to the bladder, for storage.
At the tips of each new bud, indicate their mesenchymal caps, and write that 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.
Now, re-draw the metanephric mesoderm, and indicate that, after 4 generations, (rounds) of bifurcations, the ureteric buds coalesce to form 2-4 major calyces.
In our final diagram, show that the next 4 generations of ureteric buds also coalesce, forming the minor calyces.
Indicate that 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.
Next, let's turn our attention to formation of the excretory units, aka, the nephrons.
Note that mechanisms driving the emergence of the ureteric bud from the meseonephric duct and the subsequent branching of the ureteric bud are similar.
Write that the excretory units arise from metaneprhic mesoderm, and,
That nephrogenesis continues post-natally.
We'll show four key stages of their development in three diagrams.
For context, re-draw our last diagram, and indicate that nephrogenesis occurs in the metanephric mesoderm around the collecting ducts.
The first step of nephrogenisis is renal vesicle formation.
To show this, draw a single ureteric bud; this particular bud would be the result of several rounds of bifurcations and after the establishment of the calyces.
Label the ampulla, which is its wide tip, and,
Show the mesenchymal cap.
Indicate that 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.
Next, re-draw the ureteric bud after bifurcation, and indicate that the second stage is body formation.
Show that the renal vesicle grows, transitioning first to a "comma-shaped" vesicle, (aka, body) then, to an "S-Shaped" vesicle.
Though not indicated, here, be aware that the vesicles are polarized with respect to gene expression; in other words, specific genes are expressed in specific domains.
In this same diagram, show that stage 3 is vascularization: endothelial precursors migrate to the proximal ends of the vesicles.
Finally, in stage 4, show the functional form:
Draw the ureteric bud, which is now a definitive collecting duct, and,
Connected to it, show the nephron.
At the proximal end of the nephron, indicate the glomerulus, which is a specialized "tuft" of capillaries that arose from the endothelial precursors in our previous diagram.
Surrounding the glomerulus, label the Bowman's capsule (aka, glomerular capsule).
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.