Lecture 4 Flashcards
define a morphogen
A soluble secreted molecule that acts at a distance to induce cell fates. Can induce more than one fate via its concentration gradient
What are the properties of morphogens?
They are secreted from a source and diffuse to create a concentration gradient. A particular threshold will induce a fate in a cell- cells respond in a concentration dependant manner.
What type of signal determines if a signal is a morphogen or not?
Can’t be a permissive signal= acts as a switch to allow the cell to assume the fate it was going to have. Needs to be instructive= instructs cells to take on a particular fate depending on the concentration
How do you test if a signal is permissive or instructive?
1) Place the source of the signal on the opposite side- if morphogen it will produce a mirror image of fates (instructive). If permissive the cells will assume their normal fates . e.g. Bead with shh planted in posterior limb bud= mirror image of digit formation
2) Overexpress the signal so the concentration is uniform- if morphogen = only one type of fate should be induced
What’s the difference between a bucket brigade and a type A signal?
Type A signal= morphogen= acts directly at a distance
bucket brigade= passing of message from cell to cell- each signal induces another
How do you test if a signal is bucket brigade or a morphogen?
1) create a juxtacrine ligand by added a TM domain. Signal if bucket brigade- none if morphogen
2) Make a mosaic animal where distant cells for the source don’t have an R for the ligand- bucket brigade if signal- none if morphogen
How can a steep diffusion of morphogen be created?
1) The morphogen can be guided and kept in the right direction by “sticky” ECM proteins e.g. heparan sulphate proteoglycans.
2) High concentration of Rs
How do heparan sulphate proteoglycans work and give 2 examples?
They bind to the signal to keep it in the area long enough to bind to a R. Can slow down diffusion e.g. BMP and TGFB or can facilitate diffusion e.g. hh
What is planar transcytosis and give an example
When morphogens travel through cells in a juxtacrine manner- are engulfed in vesicles and then endocytosed on the other end of the cell. E.g. dpp antibody stain shows dpp in vesicles
What is the transcriptional readout model?
The higher the concentration of morphogen the higher the concentration of morphogen which induces a particular cell fate
Describe how bicoid is a morphogen
its mRNA is localised in the drosophila embryo immediately after being laid with a higher concentration in anterior and low in posterior- diffuses into the cytoplasm and accumulates in the nucleus in a gradient throughout the embryo
How TF concentrations interpreted?
TFs have an equilibrium reaction with the DNA binding site. e.g. Can bind to gene 2 better than gene 1- in high concentrations gene 1 can activate and repress gene 2 so in low concentrations only gene2 is active= cross talk regulation
How are strict thresholds generated in steep gradients?
Positive feedback- e.g. when gene 2 is activated it can act as a TF to further activate its own expression
