2 Renal Embryology Flashcards
1
Q
Developmental events in urinary system embryogenesis
- 3 weeks
- 4 weeks
- 5 weeks
- 6 weeks
- 7 weeks
- 9-10 weeks
A
- 3 weeks
- Gastrulation
- Subdivision of the mesodermal germ layer into paraxial, intermediate, & lateral mesoderm
- 4 weeks
- Formation of the pronephric duct (–> mesonephric duct)
- Appearance & regression of pronephric tubules
- Appearance of mesonephric tubules
- 5 weeks
- Appearance of adult kindey precursors (metanephric mesenchyme & ureteric bud)
- 6 weeks
- Cranial (thoracic) mesonephros undergoes massive regression
- Caudal (lumbar) mesonephric tubules function
- Metanephric excretory units begin to form
- Kidneys begin to ascend
- 7 weeks
- Division of the cloaca complete
- Regression of the allantois
- Urogenital component of the cloacal membrane ruptures
- 9-10 weeks
- Kidneys reach a lumbar position
- Mesonephros ceases to function & regresses
- Metanephric kidney begins to produce urine
2
Q
Development of the kidneys & ureters
- Intermediate mesoderm
- Elongated duct
A
- Intermediate mesoderm (3.5 weeks)
- Extends to each side of the embryo from cervical to sacral regions
- Gives rise to 3 paired sets of excretory structures
- Only the sacral components will develop into adult kidneys
- Cervical & throaco-lumbar components are transient
- Elongated duct (4 weeks)
- Forms within the intermediate mesoderm on each side of the embryo
- Extends from the cervial region to the expanded end of the hindgut (cloaca)
- On each side of the embryo, interactions b/n this duct & the adjacent intermediate mesoderm lead to the differentiation of excretory tubules
3
Q
Kidney development
- When most events occur
- Direction of development
- Mesonephric duct
A
- When most events occur
- In the first 2 months
- Direction of development
- Cranial to caudal
- Mesonephric duct
- Long duct extending from the cervical to caudal region (claoca)
- 3 sets of nephrons/tubules
- Pronephros (top)
- Mesonephros (middle)
- Metanephros (definitive kidney + ureters)
- Metanephrogenic mesenchyme
- Ureteric bud (buds off mesonephric duct)
- Tubules next to the mesonephric duct
- Either associate w/ gonads or degenerate
- Mesonephric duct –> vas deferens, epididymis, etc. while nephrons disappear
4
Q
Pronephric kidney (pronephros)
- Consists of…
- Function
- Early stages associated duct
- Later stages associated duct
A
- Consists of small epithelial clusters (rudimentary tubules) in the cervical region
- Nonfunctional in humans
- Only present during the 4th week
- Early stages associated duct: pronephric duct
- Later stages associated duct: mesonephric (Wolffian) duct
- Primary association: mesonephros
5
Q
Mesonephric kidney (mesonephros)
- Consists of
- Associated duct
- Mesonephric tubules
- Cranial mesonephric tubules
- Caudal mesonephric tubules
A
- Consists of tubules that form a large swelling in the thoraco-lumbar region
- Associated duct: mesonephric duct
- Original pronephric duct
- Regresses in females
- forms the epididymis & vas deferens in males
- Mesonephric tubules
- Resemble simplified adult excretory tubules
- Function during 2nd month
- Cranial mesonephric tubules
- Regress shortly after they form
- Caudal mesonephric tubules
- Ultimately regress
- Some cellular components contribute to gonads in males
6
Q
Metanephric kidney (metanephros)
- General
- Two embryonic components that contribute to its formation
A
- General
- Definitive kidney
- Two embryonic components that contribute to its formation
- Ureteric bud
- Emerges as a bud off the distal end of the mesonephric duct
- Each bud penetrates intermediate mesoderm in the sacral region
- Metanephric mesenchyme (blastema)
- Intermediate mesoderm
- Ureteric bud
7
Q
Organisms that have certain kidneys
- Pronephric kidney
- Mesonephric kidney
- Metanephric kidney
A
- Pronephric kidney
- Less developed vertebrates
- Mesonephric kidney
- Amphibians & fish
- Metanephric kidney
- Humans & birds
8
Q
Development of the ureteric bud
A
- Ureteric bud emerges from the mesonephric duct
- Undergoes repeated branching & elongation
- Empties into the expanded cloaca
- Bud & branches –> ureter, renal pelvis, calyses, collecting ducts, & tubules
9
Q
Development of the metanephric mesenchyme
A
- Metanephric mesenchyme condenses around the tips of the ureteric bud & its branches
- Transforms into epithelial cells
- Differentiates into the nephrons of the kidney
- –> renal corpuscle (except blood vessels), LOH, & proximal & distal convoluted tubules
10
Q
Inductive signals
A
- Differentiation of the ureteric bud & the metanephric mesenchyme depends on mutually inductive signals
- Signals from metanephric mesenchyme –> elongation & branching of the ureteric bud
- Signals from the ureteric bud –> aggregation of metanephric mesenchyme cells & their subsequent differentiation into nephrons
11
Q
Ascent of the kidneys & arterial blood supply
A
- During 6-10 weeks (late embryogenesis)
- Kidneys ascend from a sacral to lumbar position
- During ascent, metanephric kidneys are supplied by segmental arteries that originally supplied the mesonephros
- These vessels are reduced to a single pair of renal arteries in the adult
12
Q
GNDNF-RET signaling
- GDNF (glial cell line derived growth factor)
- What limits expression/function of GDNF to sacral regions
- Hox genes
A
- GDNF (glial cell line derived growth factor)
- Secreted by metanephric mesenchyme (mesenchyme –> bud)
- Activates the RET receptor (a tyrosine kinase) & GFRA1 (its co-receptor) on mesonephric duct & ureteric bud cells
- Drives ureteric bud outgrowth & branching by influencing cell movement & proliferation
- What limits expression/function of GDNF to sacral regions
- Signaling via SLIT2 & its receptor ROBO2 repress GDNF expression at cranial levels
- BMP4 signaling inhibits RET signaling in cranial parts of the mesonephric duct
- Gremlin (BMP inhibitor) blocks BMP signaling in the metanephric mesenchyme & allows outgrowth in the region
- Hox genes (esp Hox11)
- Influence GDNF expression
- May be necessary for specifying metanephric identity (rather than pronephric or mesonephric)
13
Q
GNDNF-RET signaling mutations
- Carriers of RET or GDNF mutations
- Gene EYA1 mutations
- Gene PAX2 mutations
- Gene SALL1 mutations
- ROBO2 mutations
- BMP4 mutations
A
- Carriers of RET or GDNF mutations
- Hirschsprung disease (intestinal aganglionosis)
- Gene EYA1 mutations
- Defect: renal agenesis or hypoplasia
- Syndrome: branchio-oto-renal (BOR)
- Gene PAX2 mutations
- Defect: renal hypoplasia
- Syndrome: renal coloboma
- Expression patterns are controlled by sonic hedgehog signaling
- Gene SALL1 mutations
- Defect: renal hypoplasia
- Syndrome: townes-brocks
- Expression patterns are controlled by sonic hedgehog signaling
- ROBO2 mutations
- Vesicoureteral reflux (VUR)
- Megaureter
- Dysplastic kidneys
- BMP4 mutations
- Congenital anomalies of the kidney & urinary tract (CAKUT)
14
Q
Wnt signaling
- General
- Wnt expression
- Deregulated Wnt signaling
A
- General
- Signals from the ureteric bud influence metanephric mesenchyme development
- Signal in the opposite direction (bud –> mesenchyme) to induce nephron formation
- Wnts expressed in the ureteric bud…
- Induce metanephric mesenchyme aggregation
- Promote a mesenchymal to epithelial transition, proliferation of mesenchyme cells, & differentiation into the nephron (Wnt9b)
- Deregulated Wnt signaling –> cystic kidney diseases
- Frame shift mutation in the Wnt pathway component TCF2 –> enlarged kidnesy displaying cysts
15
Q
Wilms tumor gene 1 (WT1)
- Early stages
- Later stages
- Mutations in WT1
A
- Early stages
- Regulates GDNF
- Promotes survival of metanephric mesenchyme progenitors
- Later stages
- Inhibits proliferation of these cells –> nephron differentiation
- Develops & matures podocytes
- Mutations in WT1 –> Wilms tumors
- Most common pediatric kidney cancer
- Develop from clusters of mesenchyme (nephrogenic rests) that represent arrested nephrogenic progenitors or stem cells
- Loss of WT1 –> arrest nephron precursors in multipotent progenitor state