Lecture 5: Regulation of Kidney Development 2 Flashcards
What method can be used to visualise glomeruli and what is the marker?
Immunohistochemistry, WT-1
What analysis can be used to assess the complexity of UT branching?
Antibody analysis
What can PNA be used for?
Identify where branches and nephrons are located
What effect does BMP-4 have on branching morphogenesis?
Inhibition
What effect does DEX (glucocorticoid) have on branching morphogenesis?
Inhbition
What do glucocorticoids require?
Must be dissolved in a vehicle that is a solvent
Can the glucocorticoid vehicle regulate branching itself?
Yes
What happened when glucocorticoids were given to the mother early?
Deregulation of >1500 genes
What might happen even when you knock out a gene?
Other genes may compensate or overcompensate for the loss
Where is GDNF expressed?
Intermediate mesoderm
What is GDNF important for?
Signalling from metanephric mesenchyme to ureteric bud to signal invasion
What does GDNF act on?
c-RET (receptor)
GRF-alpha (co-receptor)
Where are the receptors for GDNF expressed?
Wolffian duct
What happens when there is a complete or partial knockout of GDNF?
- When you knockout GDNF you get complete absence of kidneys or very small kidneys
- If there is partial knockout of GDNF there is a 30% reduction in nephron number
What happens when gremlin is signalling?
No branch point is formed
What family is BMP a part of?
TGF-B
What does BMP act on?
ALK self surface receptors
What is BMP important for?
Important for growth of UB and branching morphogenesis (inhibit GDNF)
Where is BMP-4 expressed?
Along border of wolffian duct
What is the order of Wnt expression?
- Wnt11 expressed at tip of UB early in gestation
- Wnt4 expressed (pre-tubular aggregate) with Wnt11 in mid gestation
- Wnt7b then expressed
- Wnt9b expressed all of the time
What happens if Wnt is knocked out?
Reduced kidney size
How is RAS normally affected?
In a sexually dimorphic manner
What happened to sheep exposed to glucocorticoids?
Increased BP in offspring
What happened to pregnant mice that were given glucocorticoids?
Reduced nephron number in male and female offspring, increased BP in males but not females. Males had altered albuminuria and increased renal activity and renal GC activity
What is the brenner hypothesis?
Low nephron number at birth will lead to increased blood pressure and subsequent death of nephrons
What happens when you knock out Agtr1?
Vascular thickening and abnormal medulla
What happens when you knockout Agtr2?
CAKUT
