L4 - Morphogens Flashcards

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1
Q

Which two notable scientists published papers on morphogens

A

Alan turing

Lewis wolpert

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2
Q

What was Wolperts model known as

A

Positional information AKA French flag model

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3
Q

Define a morphogen

A

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

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4
Q

Which cell sees the highest concnetration of morphogen

Which cell sees the lowest

A

Cell closest to the morphogen secreting cell sees highest

Cell furthest away sees lowest

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5
Q

Morphogen secreted from _______ to the _____

A

source to sink

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6
Q

Is the morphogen gradient fixed

A

No it can change with time

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7
Q

Are all of the genes involved in patterning morphogens?

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

A

No

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

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8
Q

Describe the effect of hyperactive morphogen production in one cell

A

Information lost at one end and information gained at the other

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9
Q

Describe the effect of an ectopic source of morphogen being present

A

Information lost in the middle

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

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10
Q

What are the two major characteristics of a morphogen

A

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

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11
Q

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

A

Permissive factors

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12
Q

Morphogens are _________ signals

A

Instructive

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13
Q

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

A

For true –> duplication as high at both ends

Permissive –> no effect

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14
Q

Describe how permissive signals work

A

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

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15
Q

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

A

Shh soaked bead

Posterior region from a donor embryo

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16
Q

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

A

Duplication of the digits

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17
Q

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

A

Keep the one signal at uniform concentration

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18
Q

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

A

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

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19
Q

Permissive signalling is concnetration ..

A

Independent

20
Q

Instructive signalling is concentration

A

Dependent

21
Q

Describe how morphogen signalling differs from the bucket brigade

A

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

22
Q

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

A

For a morphogen only the adjacent cell would diff

In bucket bridgade - normal

23
Q

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

A

Juxtacrine

24
Q

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

A

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

25
Q

Why is passive diffusion not suitable for establishing a morphogen gradient

A

The gradient created would be too shallow

26
Q

How can steep gradients be created (3)

A

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

27
Q

What is HSPG

A

Heparan suplhate proteoglycan

28
Q

What are HSPGs also known as

A

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

29
Q

How do HSPGs regulate morphogen diffusion

A

Sequestration or slowing diffusion

Fascillitating diffusion

30
Q

Sequestration or slowing diffusion is seen in which pathway

A

BMP

31
Q

Fascilitating diffusion by HSPGs is seen in which pathway

A

Hh

32
Q

What two binding sites do ligands commonly have

A

HSPG binding site and receptor binding site

THESE ARE AT TWO DIFFERENT LOCATIONS ON THE LIGAND

33
Q

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

A

Low affinity

34
Q

Describe planar transcytosis

A

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

35
Q

Describe the evidence for planar transcytosis

A

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

36
Q

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

A

A mechanism to stop cells prematurely differentiating

37
Q

What does the cell wait for before it differentiates

A

Steady state to be reached

38
Q

A higher morphogen concentration would mean …

A

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

39
Q

Descirbe the localisation of bicoid mRNA in the egg

A

Localised at the anterior

40
Q

Once translated where does bicoid diffused

A

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

41
Q

Bicoid is both a ____________ and __________

A

Morphogen and a transcription factor

42
Q

Enhancer elements can have different ________ for the Tf

A

Affinties

43
Q

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

A

Enhancers have a lower affinity

So high conc of morphogen is required for this to be overcome

44
Q

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

A

Enhancer has a higher affinity

Hence a higher concentration of TF is required to overcome this

45
Q

TF binding is

A

Transient

46
Q

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

A

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