Morphogens

Question 1

When was the first concept of morphogens published?

Answer 1

1952
In 1969 paper published hypothetical approach about how they worked

Question 2

What is a morphogen?

Answer 2

Soluble secreted molecule that acts at a distance to specify the fates of cells through a concentration gradient

Question 3

What are the requirements for a morphogen?

Answer 3

• Induce different outputs at different concentrations
• Act directly at a distance
• can only operate with production AND destruction

Question 4

How do we know that the morphogen is instructive and not permissive?

Answer 4

i.e. do xyz now / or do what you knew you were going to do already now im here

• Put morphogen at ectopic location e.g. BMPs on both sides of the mesoderm
• If it was a permissive signal then it wouldn’t matter how much morphogen each cell gets to go to its ‘predetermined fate’.
• Obvs its not so it changes the fate of the cell

Question 5

Give an example of putting a morphogen at an ectopic location to see its effects

Answer 5

• bead soaked in Shh planted in an ectopic portion (anterior)
• Two wings were produced due to new source of morphogen
• Mirror image of wins above and below

Question 6

How else can we use experiments to see if a morphogen is instructive and not permissive?

Answer 6

(referring to the image in lecture)
- Provide red cell signal at uniform concentrations e.g. give all the cells the conc. Of the morphogen that the blue cell gets and if its an instructive signal then all cells will go blue
- Permissive would = no effect

Question 7

What is the bucket brigade theory?

Answer 7

States that each signal from a cell induces another instead of morphogens acting directly at a distance

Question 8

How is the bucket brigade theory tested against?

Answer 8

• Tag protein so it gets stuck in producing cell
• Only next cell sees it
• Morphogen = nothing happens after because it hasn’t been exposed to subsequent cells
• Permissive= all cells differentiate due to ‘cascade’
  Can also do this by removing morphogen receptor from cells so they cant respond

Question 9

Why has passive diffusion been dismissed as the mechanism for establishing a morphogen gradient?

Answer 9

• Purely passive would mean 3 dimensional diffusion
• Only a tiny amount of the morphogen would diffuse in the desired way and the same effects would occur around the full rotation of the secreting cell

Question 10

What is the transport mechanism theory for establishing a morphogen gradient?

Answer 10

• Morphogen is trapped in the extracellular space by HSPGs which keeps it on the cell surface where it is ready to be read
• ‘restricted diffusion’ ‘//facilitated diffusion’

Question 11

What is meant by planar transcytosis?

Answer 11

• Morphogen is taken in to the cell and trafficked by vesicles so the morphogen can travel through the cell (edocytosis)
• Proven as morphogen gradient cell breaks down when endocytic machinery is removed

Question 12

How do we block premature specification? (issue with experimental evidence and timing)

Answer 12

Thresholds, each differentiating cell has a threshold of the amount of morphogen it needs

Question 13

What is the transcription read-out model?

Answer 13

• Higher conc. of morphogen often results in a higher concentration of an activated transcription factor
• Because there are low and high affinity sites, less morphogen means only high affinity sites will be bound to
• With high conc. there are also low affinity sites that are bound to at differing levels depending on amount of morphogen causing differential differentiation

Question 14

Why do the cells further along the gradient not have characteristics from the cells before it?

Answer 14

One of the differentiation fates is to encode a repressor
So high morphogen switches on green genes which switches off blue genes
-Also genes which are involved in positive feedback, to enhance the identity of the cell fate