Morphogens Flashcards
What is a morphogen?
A soluble secreted molecule that acts at a distance to specify the fates of cells. They may specify more than one cell type by creating a concentration gradient
What are the two things that a morphogen must do?
Induce different outputs at different concentrations
Act directly at a distance
How can you test between an instructive signal (morphogen) and a permissive signal?
- Provide a second source of the signal. The instructive signal will create a mirror image but there will be no effect from the permissive signal
- Provide the original signal at a uniform concentration. In the morphogen this will induce one cell type. In the permissive signal there will be no effect
What is the experimental example of a morphogen producing a mirror image when there is a second source as the morphogen?
The chick wing with ectopic Shh
How can you test between a morphogen with a ligand that acts directly at a distance or cells that use bucket brigade signalling?
- Use genetic engineering to make the proposed morphogen a juxtacrine
In the morphogen only the neighbouring cell will be affected and be converted to its fate
Bucket brigade will not be affected - Make a genetic mosaic that lacks a receptor for the original ligand on one cell
One cell won’t have its fate in morphogen
Bucket brigade won’t be affected except the neighbouring cell if it lacked a receptor
Is passive diffusion what causes a morphogen gradient?
Passive diffusion would only generate a shallow gradient
What is restricted diffusion?
Generation of a steep gradient by binding to molecules in the extracellular matrix and high concentrations of the receptor. Rapid degradation of the signal in the extracellular space may also generate a steep gradient
What is the role of heparan sulfate proteoglycans in signalling?
They are found in the ECM and bind to ligands. They regulate morphogen diffusion by sequestration or slowing diffusion (BMP)/facilitating diffusion (Hh)
How does planar transcytosis play a role in establishing a morphogen gradient?
A pit is formed in the cell membrane that engulfs the morphogen in a vesicle
Repeated cycles of endocytosis and resecretion allows certain morphogens to travel through the cells in a tissue
What is the evidence for transcytosis in Dpp signalling?
Antibody staining shows that Dpp is present in vesicles
Mutations that block vesicle formation cause Dpp to act in a juxtacrine manner
Describe the transcriptional read out model
Different concentrations of morphogens in initially identical cells leads to different concentrations of the activated transcription factor
Higher concentration means more TF
What is the role of Bicoid as both a morphogen and a transcription factor?
Bicoid mRNA is localised at the anterior of the egg and translated into protein during early embryogenesis
The Bicoid protein then diffuses through the cytoplasm and accumulates in the nuclei of the syncytial blastoderm, generating a concentration gradient
How does the transcriptional activation of two neighbouring cells differ at different concentrations of TF?
Medium TF concentration:
One cell will have a low affinity receptor and the other a high affinity receptor
Only the cell with the high affinity enhancer can bind enough TF to activate gene expression
High TF concentration:
Both high affinity enhancers and low affinity enhancers are activated
How can the low affinity enhancer cells block gene expression of the high affinity enhancer cells? (Crosstalk)
The cell with low affinity has genes that code for a repressor
High level of morphogen = genes turned on and repress the genes of the high affinity cell
Describe positive feedback regulation
It helps cells commit to their fate as the gene encodes a transcription factor that activates its own expression
