L4 - Morphogens

Question 1

Which two notable scientists published papers on morphogens

Answer 1

Alan turing

Lewis wolpert

Question 2

What was Wolperts model known as

Answer 2

Positional information AKA French flag model

Question 3

Define a morphogen

Answer 3

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

Question 4

Which cell sees the highest concnetration of morphogen

Which cell sees the lowest

Answer 4

Cell closest to the morphogen secreting cell sees highest

Cell furthest away sees lowest

Question 5

Morphogen secreted from _______ to the _____

Answer 5

source to sink

Question 6

Is the morphogen gradient fixed

Answer 6

No it can change with time

Question 7

Are all of the genes involved in patterning morphogens?

What is an example of a patterning molecule that is NOT a morphogen

Answer 7

No

BMPs during dorsalisation of the neural tube - many different BMPs secreted each capable of instructing a certain cell type

Question 8

Describe the effect of hyperactive morphogen production in one cell

Answer 8

Information lost at one end and information gained at the other

Question 9

Describe the effect of an ectopic source of morphogen being present

Answer 9

Information lost in the middle

duplication of either ends with the lowest extreme being lost all together

Question 10

What are the two major characteristics of a morphogen

Answer 10

Must be able to induce different outputs at different concentrations
Must be able to act directly at a distance

Question 11

What are factors that cause differentiation of cells which already know their fate called

Answer 11

Permissive factors

Question 12

Morphogens are _________ signals

Answer 12

Instructive

Question 13

What would be seen when grafting the ‘morphogen producing cell’ ectopicially in both a true morphogen system and in a permissive system

Answer 13

For true –> duplication as high at both ends

Permissive –> no effect

Question 14

Describe how permissive signals work

Answer 14

Presence of the signal tells the cells to differentiate but they ALREADY KNOW THEIR FATE.

Question 15

What could be used as a graft in the chick limb bud graft

Answer 15

Shh soaked bead

Posterior region from a donor embryo

Question 16

Describe the results of the ectopic graft of posterior region in chick limb bud to the anterior

Answer 16

Duplication of the digits

Question 17

Apart from ectopic studies how else could you test for the difference between instructive and permissive signalling?

Answer 17

Keep the one signal at uniform concentration

Question 18

Describe the effects of keeping the concnetration set in both a morphogen and permissive system

Answer 18

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

Question 19

Permissive signalling is concnetration ..

Answer 19

Independent

Question 20

Instructive signalling is concentration

Answer 20

Dependent

Question 21

Describe how morphogen signalling differs from the bucket brigade

Answer 21

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

Question 22

Describe how tethering the molecule to the membrane would differentiate between bucket brigade and morphogen

Answer 22

For a morphogen only the adjacent cell would diff

In bucket bridgade - normal

Question 23

If the molecule was tethered at the membrane what would the type of signalling be used

Answer 23

Juxtacrine

Question 24

How could a genetic mosaic be used to differnetiate between morphogen and bucket brigade

Answer 24

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

Question 25

Why is passive diffusion not suitable for establishing a morphogen gradient

Answer 25

The gradient created would be too shallow

Question 26

How can steep gradients be created (3)

Answer 26

The binding to molecules present in the ECM High concentrations of the receptor Rapid degredation of the signal

Question 27

What is HSPG

Answer 27

Heparan suplhate proteoglycan

Question 28

What are HSPGs also known as

Answer 28

Co-receptors --> EXCEPT they dont cause any kind of response

Question 29

How do HSPGs regulate morphogen diffusion

Answer 29

Sequestration or slowing diffusion | Fascillitating diffusion

Question 30

Sequestration or slowing diffusion is seen in which pathway

Answer 30

BMP

Question 31

Fascilitating diffusion by HSPGs is seen in which pathway

Answer 31

Hh

Question 32

What two binding sites do ligands commonly have

Answer 32

HSPG binding site and receptor binding site THESE ARE AT TWO DIFFERENT LOCATIONS ON THE LIGAND

Question 33

What can be said of the affinity of the HSPG binding site

Answer 33

Low affinity

Question 34

Describe planar transcytosis

Answer 34

repeated cycles of endocytosis and re-secretion allows certain molecules to travel through cells in a tisssue

Question 35

Describe the evidence for planar transcytosis

Answer 35

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

Question 36

Equillbrium in a morphogen takes time to establish so what is required

Answer 36

A mechanism to stop cells prematurely differentiating

Question 37

What does the cell wait for before it differentiates

Answer 37

Steady state to be reached

Question 38

A higher morphogen concentration would mean ...

Answer 38

A higher concentration of the activated TF in the nucleus of the cell

Question 39

Descirbe the localisation of bicoid mRNA in the egg

Answer 39

Localised at the anterior

Question 40

Once translated where does bicoid diffused

Answer 40

Through the cytoplasm and accumulates in the nuclei of the synvytial blastoderm generating a concentration gradient

Question 41

Bicoid is both a ____________ and __________

Answer 41

Morphogen and a transcription factor

Question 42

Enhancer elements can have different ________ for the Tf

Answer 42

Affinties

Question 43

Describe the affinity of an enchance which require high levels of morphogen What is the logic to this?

Answer 43

Enhancers have a lower affinity | So high conc of morphogen is required for this to be overcome

Question 44

Describe the affinity of an enhancer which requires low levels of morphogen for it to become activated

Answer 44

Enhancer has a higher affinity | Hence a higher concentration of TF is required to overcome this

Question 45

TF binding is

Answer 45

Transient

Question 46

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

Answer 46

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