Lecture 5: Regulation of Kidney Development 2

Question 1

What method can be used to visualise glomeruli and what is the marker?

Answer 1

Immunohistochemistry, WT-1

Question 2

What analysis can be used to assess the complexity of UT branching?

Answer 2

Antibody analysis

Question 3

What can PNA be used for?

Answer 3

Identify where branches and nephrons are located

Question 4

What effect does BMP-4 have on branching morphogenesis?

Answer 4

Inhibition

Question 5

What effect does DEX (glucocorticoid) have on branching morphogenesis?

Answer 5

Inhbition

Question 6

What do glucocorticoids require?

Answer 6

Must be dissolved in a vehicle that is a solvent

Question 7

Can the glucocorticoid vehicle regulate branching itself?

Answer 7

Yes

Question 8

What happened when glucocorticoids were given to the mother early?

Answer 8

Deregulation of >1500 genes

Question 9

What might happen even when you knock out a gene?

Answer 9

Other genes may compensate or overcompensate for the loss

Question 10

Where is GDNF expressed?

Answer 10

Intermediate mesoderm

Question 11

What is GDNF important for?

Answer 11

Signalling from metanephric mesenchyme to ureteric bud to signal invasion

Question 12

What does GDNF act on?

Answer 12

c-RET (receptor)

GRF-alpha (co-receptor)

Question 13

Where are the receptors for GDNF expressed?

Answer 13

Wolffian duct

Question 14

What happens when there is a complete or partial knockout of GDNF?

Answer 14

• 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

Question 15

What happens when gremlin is signalling?

Answer 15

No branch point is formed

Question 16

What family is BMP a part of?

Answer 16

TGF-B

Question 17

What does BMP act on?

Answer 17

ALK self surface receptors

Question 18

What is BMP important for?

Answer 18

Important for growth of UB and branching morphogenesis (inhibit GDNF)

Question 19

Where is BMP-4 expressed?

Answer 19

Along border of wolffian duct

Question 20

What is the order of Wnt expression?

Answer 20

• 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

Question 21

What happens if Wnt is knocked out?

Answer 21

Reduced kidney size

Question 22

How is RAS normally affected?

Answer 22

In a sexually dimorphic manner

Question 23

What happened to sheep exposed to glucocorticoids?

Answer 23

Increased BP in offspring

Question 24

What happened to pregnant mice that were given glucocorticoids?

Answer 24

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

Question 25

What is the brenner hypothesis?

Answer 25

Low nephron number at birth will lead to increased blood pressure and subsequent death of nephrons

Question 26

What happens when you knock out Agtr1?

Answer 26

Vascular thickening and abnormal medulla

Question 27

What happens when you knockout Agtr2?

Answer 27

CAKUT