Lecture 9

Question 1

What happens to the offspring of sheep who ate corn lillies? What is the compound that causes the phenotype?

Answer 1

Cyclopic lambs due to cyclopamine

Question 2

Give an example of a vertebrate homolog of Hh. When were most of the homologs identified?

Answer 2

Shh, Ihh, ect. Most were Identified in the 80’s (hence Sonic Hh)

Question 3

Briefly describe the Hh signalling pathway

Answer 3

Ptch1 is a membrane receptor that normally inhibits smoothened, keeping TF Gli out of the nucleus. When Hh (a signalling molecule) binds to Ptch1 it inhibits the receptor which then inhibits the inhibition of Smo. Gli then enters the nucleus and the downstream genes of the pathway can be transcribed.

Question 4

What was the main hypothesis surround Hh signalling and cyclopia? How did this arise?

Answer 4

HYPOTH: Cyclopamine antag Shh or element of Shh pathway

L.O.F. mut of Shh/Shh signalling led to the same phenotype as those involved in cyclopamine-related cases

Question 5

TRUE OR FALSE

Shh is important for developmental processes and in stem cells proliferation and self-renewal?

Answer 5

True

Question 6

Where do cancers that have dysregulation of Shh tend to develop?

Answer 6

1. Where Shh is involved in developmental manner

2. Where Shh levels are normally held at a careful balance

Question 7

What sort of smoothened mutation leads to BCC?

Answer 7

An activating smo mutation, or any mutation that leads to the activation of the Hh signalling pathway

Question 8

Can an oncogenic mutation in smoothened by reversed by cyclopamine?

Answer 8

Yes. As cyclopamine blocks the Hh signalling pathway it can be used against an activating mutation