Clinical Applications of Developmental Biology

Question 1

Why do we need animal models of human disease?

Answer 1

Understanding disease mechanisms
Development of diagnostic tools
Development of therapeutics

Question 2

Hedgehog signalling pathway in vertebrates

Answer 2

Ptc inhibits smo
When SHH binds to ptc, stimulates gli
Gli goes into nucleus –> transcription enabled

Question 3

Where is SHH expressed?

Answer 3

• Notochord (a cartilaginous skeletal rod supporting the body in all embryonic and some adult chordate animals.)
• Floorplate (structure integral to the developing nervous system of vertebrate organisms)
• ZPA of limb bud

Question 4

What does overactivity of Hedgehog signalling lead to?

Answer 4

Extra digits

Question 5

What is preaxial polydactyl?

Answer 5

Where the extra digit is towards the first digit of the hand/foot

Question 6

What is holoprosencephaly?

Answer 6

The prosencephalon fails to develop into two hemispheres –> range of midline malformations

Question 7

What is holoprosencephaly caused by?

Answer 7

Dominant mutations in the sonic hedgehog gene –> loss of Hedgehog signalling

Question 8

What is cycloplamine?

Answer 8

A steroid alkaloid isolated from the Californian corn lily

Question 9

What does cyclopamine cause?

Answer 9

Cyclopia

Question 10

How does cyclopamine cause cyclopia in the early embryo?

Answer 10

Teratogenic effect mimics the genetic loss of Shh function

Question 11

Define teratogenic

Answer 11

An agent or factor that causes malformation of an embryo

Question 12

How does cyclopamine mimic the loss of Shh function?

Answer 12

Blocks the Hedgehog signalling pathway by inhibiting the Smo protein

Question 13

Which protein does cyclopamine block?

Answer 13

Smoothened

Question 14

Adenomatous polyposis coli (APC) and colon cancer can be caused by inappropriate activation of which pathway?

Answer 14

The Wnt signalling pathway

Question 15

What can inappropriate activation of the Wnt signalling pathway cause?

Answer 15

Adenomatous polyposis coli and colon cancer

Question 16

Inappropriate activation of the development signalling pathway can cause?

Answer 16

Basal cell carcinoma (type of skin cancer)

Question 17

Tumours share characters with _______ cells

Answer 17

Embryonic

Question 18

Characteristics of tumours

Answer 18

• Rapidly dividing
• Undifferentiated
• Undergo epithelial to mesenchymal transition

Question 19

What is name given for the transition from epithelium to mesenchyme?

Answer 19

Metastasis

Question 20

Tumours don’t follow the normal controls on:

Answer 20

• Proliferation
• Differentiation
• Growth

Question 21

In which genes can mutations cause cancer?

Answer 21

Proto-oncogenes and tumour suppressor genes

Question 22

Give an example of a proto-oncogene

Answer 22

Smo

Question 23

Give an example of a tumour suppressor gene

Answer 23

Ptc

Question 24

What kind of mutations in proto-oncogenes can cause cancer?

Answer 24

Gain-of-function mutations

Question 25

What kind of mutations in tumour suppressor genes can cause cancer?

Answer 25

Loss-of-function mutations

Question 26

What kind of treatments are being developed for cancer caused by over activation of Hedgehog signalling?

Answer 26

Small molecule inhibitors of Hedgehog signalling