Morphogens

Question 1

what does the presence of several thresholds within a morphogen gradient enable?

Answer 1

decision making so that clearly defined cell fates can be established.

Question 2

Name 2 requirements of a morphogen, and 2 tests for each requirement.

Answer 2

Induce different outputs at different concentrations

• morphogens are instructive not permissive signals
  1. provide an ectopic source of the potential morphogen
• if signal is instructive, a mirror image in the field of cells will be produced
• • if the signal is permissive there will be no effect.*
    2. provide the signal in a uniform concentration
• • if the signal is instructive, then all cells will adopt the same fate*
• • if the signal is permissive then there will be no effect.*

Act Directly at a distance

• morphogens do not act as a bucket brigade (an instructive signal acts paracrinely on its neighbour. the neighbour produces a signal which too acts paracrinely on its neighbouring cell)
  1. genetically engineer the potential morphogen to be juxtacrine.
• • if signal is a morphogen, then only the neighbouring cell to the instructive cell will differentiate*
• • if the signal acts as a bucket brigade, there will be no effect*
    2. make one of the cells in the field lack the receptor for the potential morphogen
• • if the signal is a morphogen, then all cells except the one that lacks the receptor will differentiate*
• • if the signal acts as a bucket brigade, then there will be no effect, except if the first cell in the ‘chain’ lacks the receptor.*

Question 3

1. what type of gradient is established by passive diffusion?
2. name 2 ways in which a steep gradient is established, and how these methods do so.
3. how do HSPGs influence the formation of the morphogen gradient?
4. what is planar transcytosis, and name a morphogen which diffuses in this way
5. when is it likely that cells respond to the morphogen and why?

Answer 3

1. shallow
2. a high number of receptors and the interraction of morphogens with the extracellular matrix. this slows the morphogen down.
3. they are co-receptors thus bind to non-competitive sites on morphogens. They either facilitate or sequestrate diffusion
4. the active transport of ligands through cells. the morphogen is endocytosed into the cell and then exocytosed on the opposite side. dpp travels in this way.
5. when steady state receptor activation occurs, in order to prevent premature differentiation. This is because cells that are closer to the instructive cell will be exposed to many thresholds as the gradient is being established.

Question 4

1. what do higher morphogen concentrations lead to?
2. what is the affinity that enhancers that regulate green genes for TFs compared to those of blue genes?
3. describe how the gradient interpreted?

Answer 4

1. higher concentration of activated TFs
2. lower affinity
3. medium morphogen concentration leads to medium TF activation. Blue cells are exposed to this concentration, and it is sufficient to activate blue genes, but not green genes. Green genes are exposed to high morphogen concentration, which causes high TF activation. This is sufficient to activate both blue and green genes. The green gene product encodes a repressor of blue genes and an enhancer of green genes so only one fate decision is made.