Morphogens

Question 1

What is the definition of a morphogen?

Answer 1

A soluble secreted molecule which acts at a distance to specify the fates of cells. A morphogen may specify more than one cell type by forming a concentration gradient

Question 2

What is morphogenesis?

Answer 2

The creation of shape

Question 3

Which two people suggested the presence of morphogens?

Answer 3

AM Turing - The chemical basis of morphogenesis 1951

Lewis Wolpert - Positional Information and the Spatial Patterning of Cellular Differentiation 1969

Question 4

A morphogen could either be….

Answer 4

An instructive signal
OR
A permissive signal

Question 5

How can we test if a ligand is a morphogen?

Answer 5

Using ectopic expression:
Morphogens cause a mirror image to be created if expressed ectopically
Eg ZPA in the chick limb bud creates a mirror image as Shh is a morphogen

Question 6

What would happen if you exposed all cells to the same level of morphogen?

Answer 6

All cells would acquire the same fate

Question 7

What are the two models for how morphogens move through tissues?

Answer 7

1) The ligand diffuses from the source cell

2) There is a ‘bucket brigade’ ie like chinese whispers

Question 8

How can we show the bucket brigade system is not use by morphogens?

Answer 8

Test 1) Use genetic engineering to make the proposed molecule juxtacrine
This would not affect ligands using the bucket brigade model but the cells do not acquire their normal fates showing that morphogens diffuse
Test 2) Make a genetic mosaic that lacks a receptor for the source signal in one of the cells
All cells differentiate except the one without the receptor - if the BB system was used there would be no effect

Question 9

How can the morphogen gradient be enhanced?

Answer 9

Morphogen binds to molcules in the ECM eh heparan sulphate proteoglycans

Question 10

What is it called when morphogen gradients are made steeper?

Answer 10

Restriction diffusion

Question 11

How else could the gradient be made steeper?

Answer 11

Rapid degeneration

Question 12

HSPGs can also be called what?

Answer 12

co-receptors

Question 13

How do HSPGs regulate morphogen diffusion?

Answer 13

Sequestering or slowing diffusion eg BMP

Facilitating Diffusion eg Hedgehog

Question 14

What is planar transcytosis?

Answer 14

Plays a role in establishing gradients when a pit forms in the cell membrane and engulfs the morphogen in a vesile

Question 15

What is the evidence for planar transcytosis in Dpp signalling?

Answer 15

Antibody staining shows Dpp is found in vesicles

Mutations that block vesicle formation cause Dpp to act in a juxtacrine manner