L4 - Morphogens Flashcards
Which two notable scientists published papers on morphogens
Alan turing
Lewis wolpert
What was Wolperts model known as
Positional information AKA French flag model
Define a morphogen
A morphogen is a soluble secreted molecule which acts at a distance to specify cell fates
The morphogen may specify more than one cell type by forming a concentration gradient
Which cell sees the highest concnetration of morphogen
Which cell sees the lowest
Cell closest to the morphogen secreting cell sees highest
Cell furthest away sees lowest
Morphogen secreted from _______ to the _____
source to sink
Is the morphogen gradient fixed
No it can change with time
Are all of the genes involved in patterning morphogens?
What is an example of a patterning molecule that is NOT a morphogen
No
BMPs during dorsalisation of the neural tube - many different BMPs secreted each capable of instructing a certain cell type
Describe the effect of hyperactive morphogen production in one cell
Information lost at one end and information gained at the other
Describe the effect of an ectopic source of morphogen being present
Information lost in the middle
duplication of either ends with the lowest extreme being lost all together
What are the two major characteristics of a morphogen
Must be able to induce different outputs at different concentrations
Must be able to act directly at a distance
What are factors that cause differentiation of cells which already know their fate called
Permissive factors
Morphogens are _________ signals
Instructive
What would be seen when grafting the ‘morphogen producing cell’ ectopicially in both a true morphogen system and in a permissive system
For true –> duplication as high at both ends
Permissive –> no effect
Describe how permissive signals work
Presence of the signal tells the cells to differentiate but they ALREADY KNOW THEIR FATE.
What could be used as a graft in the chick limb bud graft
Shh soaked bead
Posterior region from a donor embryo
Describe the results of the ectopic graft of posterior region in chick limb bud to the anterior
Duplication of the digits
Apart from ectopic studies how else could you test for the difference between instructive and permissive signalling?
Keep the one signal at uniform concentration
Describe the effects of keeping the concnetration set in both a morphogen and permissive system
In morphogen system only one cell type would be specified - the one specified by the particular cncnetration of the morphogen
In permissive there would be no effect
Permissive signalling is concnetration ..
Independent
Instructive signalling is concentration
Dependent
Describe how morphogen signalling differs from the bucket brigade
Bucket brigade Cell A produces A signal induces Cell B
Cell B produces B signal induced Cell C
Etc …..
Morphogen X conc of A = cell A
y conc of A = cell B
z conc of A = cell C
Describe how tethering the molecule to the membrane would differentiate between bucket brigade and morphogen
For a morphogen only the adjacent cell would diff
In bucket bridgade - normal
If the molecule was tethered at the membrane what would the type of signalling be used
Juxtacrine
How could a genetic mosaic be used to differnetiate between morphogen and bucket brigade
Make mosaic that lacks the receptor for red signal in one of the cells
Bucket brigade - normal
Morphogen - cell with the receptor missing would not differentiate - other cell types would
Why is passive diffusion not suitable for establishing a morphogen gradient
The gradient created would be too shallow
How can steep gradients be created (3)
The binding to molecules present in the ECM
High concentrations of the receptor
Rapid degredation of the signal
What is HSPG
Heparan suplhate proteoglycan
What are HSPGs also known as
Co-receptors –> EXCEPT they dont cause any kind of response
How do HSPGs regulate morphogen diffusion
Sequestration or slowing diffusion
Fascillitating diffusion
Sequestration or slowing diffusion is seen in which pathway
BMP
Fascilitating diffusion by HSPGs is seen in which pathway
Hh
What two binding sites do ligands commonly have
HSPG binding site and receptor binding site
THESE ARE AT TWO DIFFERENT LOCATIONS ON THE LIGAND
What can be said of the affinity of the HSPG binding site
Low affinity
Describe planar transcytosis
repeated cycles of endocytosis and re-secretion allows certain molecules to travel through cells in a tisssue
Describe the evidence for planar transcytosis
In dpp signalling
Ab staining shows Dpp is found in vesciles
IMPORTANTLY mutations that block vesicle formation cause Dpp to act in a juxtacrine manner
Equillbrium in a morphogen takes time to establish so what is required
A mechanism to stop cells prematurely differentiating
What does the cell wait for before it differentiates
Steady state to be reached
A higher morphogen concentration would mean …
A higher concentration of the activated TF in the nucleus of the cell
Descirbe the localisation of bicoid mRNA in the egg
Localised at the anterior
Once translated where does bicoid diffused
Through the cytoplasm and accumulates in the nuclei of the synvytial blastoderm generating a concentration gradient
Bicoid is both a ____________ and __________
Morphogen and a transcription factor
Enhancer elements can have different ________ for the Tf
Affinties
Describe the affinity of an enchance which require high levels of morphogen
What is the logic to this?
Enhancers have a lower affinity
So high conc of morphogen is required for this to be overcome
Describe the affinity of an enhancer which requires low levels of morphogen for it to become activated
Enhancer has a higher affinity
Hence a higher concentration of TF is required to overcome this
TF binding is
Transient
How do cells block gene expression -
i.e. in a cell which requires high levels of morphogen - why arent genes which require lower levels of morphogen expressed
encoding of a repressor
In cell that requires highest level of morphogen
gene encodes a repressor which represseses genes that are activated at lower concnetrations of morphogen
