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211: Cell Biology > 19. Hedgehog & Wnt signalling > Flashcards

19. Hedgehog & Wnt signalling Flashcards

1
Q

what type of structure is a denticle

A

a bristle like structure

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2
Q

where are denticles present in drosophila

A

present on the anterior half - posterior half is smooth

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3
Q

who identified segment polarity mutants

A

Volhard & Wieschaus

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4
Q

describe segment polarity mutants in drosophila

A

a group of mutants that affected the patterning within segments of the drosophila body

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5
Q

what do hedgehog genes do

A

produces hedgehog proteins that are morphogens - signalling proteins involved in embryonic development

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6
Q

how many types of hedgehog proteins in drosophila

A

1

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7
Q

how many types of hedgehog proteins in vertebrates

A

3

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8
Q

name the hedgehog proteins found in vertebratea

A

sonic, indian, desert

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9
Q

what modifies hedgehog proteins

A

cleavage and addition of cholesterol

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10
Q

define morphogen

A

signalling proteins involved in embryonic development

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11
Q

what is the purpose of cholesterol in relation to hedgehog

A

embeds hedgehog in the in the cell membrane

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12
Q

what is the role of wingless

A

switch on expression of hedgehog in the adjacent stripe

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13
Q

how are drosophila embryo segments marked out

A

alternating expression of wingless (black) and hedgehog (red)

= red and black stripes

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14
Q

what is the boundary between the wingless and hedgehog stripes called

A

the parasegment boundary

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15
Q

what does hedgehog do in its segment

A

induces diffusible wingless in the adjacent cell

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16
Q

what happens if hedgehog lacks cholesterol

A

it is capable to diffuse - this means it can switch on wingless in more cells

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17
Q

describe the hedgehog receptor

A

patches

= 12 transmembrane domain

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18
Q

how does patched work

A

the KO of patched activates the hedgehog response - involved smoothened (Smo) protein

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19
Q

what happens in the absence of hedgehog (Hh)

A

patched receptors hide smoothened protein in vesicles

Ci/Cos2/Fu forms a complex on microtubules = Ci is phosphorylated by protein kinase A

Ci enters and inhibits transcription

20
Q

what happens in the presence of hedgehog (Hh)

A

Hh binds to patched receptor

smoothened (Smo) moves to the plasma membrane

Smo interacts with Cos2/Fu = dissociates from microtubules

Cos2/Fu is phosphorylates

unphosphorylated Ci moves to the nucleus = binds CBP and activates target genes

21
Q

what does the nervous system form from

A

ectoderm

- overlying the notochord

22
Q

what secretes sonic hedgehog (Shh)

A

the notochord

23
Q

what does Shh induce

A

the floor plate which secretes further Shh

24
Q

at high concentrations of Shh, what is specified

A

motoneurons

25
Q

what is specified at medium Shh conc

A

V2 interneurons

26
Q

what is specified at low Shh conc

A

V1 interneurons

27
Q

how can Hh signalling lead to cancer

name a specific cancer

A

Hh stimulates stem cell proliferation in the basal layer of skin

excess Hh leads to over proliferation
= basal cell carcinoma

28
Q

name a tumour suppressor that acts against Hh

A

Ptc1

29
Q

how does Ptc1 inhibit Hh

A

inhibits Hh signalling

30
Q

who is particularly vulnerable to Basal cell carcinoma, why?

A

Gorlin’s syndrome

- they have mutated patched receptors

31
Q

what could be a potential therapeutic avenue for treating some cancers

A

anti-cancer drugs based on molecules that inhibit Hh signalling

32
Q

what are Wnt proteins involved in (2)

A

cell cycle regulation

immune cell maintenance

33
Q

what is the name Wnt an amalgamation off

A

wingless (segment polarity gene)

Int (mouse gene)

34
Q

how many types of Wnt in:
humans
drosophila

A

11-12

1

35
Q

describe the structure of Wnt

A

many cysteines

36
Q

what is the benefit of there being many cysteines in Wnt

A

allows them to form intra-chain disulphide bonds that increase stability

37
Q

like Hh - Wnt is modified:

what modifies Wnt
how is it modified

A

modified by porcupine enzyme

fatty acid palmitoleate is added to the conserved serine

38
Q

what are the two receptors for Wnt

A

LRP

frizzled

39
Q

describe what happens in the absence of Wnt

A

LRP is not phosphorylated

cytoplasmic complex phosphorylates beta-catenin

beta-catenin is then targeted for proteosomal degradation

TCF represses transcriptional targets

40
Q

describe what happens in the presence of Wnt

A

Wnt binds to LRP and frizles

LRPs cytoplasmic tail phosphorylates axin

beta catenin is released from the axin held complex

beta catenin translocates to the nucleus - binds to TCF = activating transcription of target genes

41
Q

what is the role of wingless

A

to induce Hh expression in adjacent cells

42
Q

what is an essential function of Wnt

A

establishing the nieuwkoop centre

43
Q

what can be done to induce a second nieuwkoop centre to form

A

add beta-catenin mRNA to the ventral side = second centre and duplicated axis of development

44
Q

what can over-expression of Wnt cause

A

cancer

45
Q

how can Wnt’s cause cancer

A

loss of APCs = excess Wnt signalling

prevent beta-catenin degradation = prolonged over expression of genes

46
Q

what mediates the destruction of beta-catenin

A

APCs

47
Q

what does APC stand for

A

adenomatous polyposis coli

211: Cell Biology (20 decks)

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