19. Hedgehog & Wnt signalling

Question 1

what type of structure is a denticle

Answer 1

a bristle like structure

Question 2

where are denticles present in drosophila

Answer 2

present on the anterior half - posterior half is smooth

Question 3

who identified segment polarity mutants

Answer 3

Volhard & Wieschaus

Question 4

describe segment polarity mutants in drosophila

Answer 4

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

Question 5

what do hedgehog genes do

Answer 5

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

Question 6

how many types of hedgehog proteins in drosophila

Answer 6

1

Question 7

how many types of hedgehog proteins in vertebrates

Answer 7

3

Question 8

name the hedgehog proteins found in vertebratea

Answer 8

sonic, indian, desert

Question 9

what modifies hedgehog proteins

Answer 9

cleavage and addition of cholesterol

Question 10

define morphogen

Answer 10

signalling proteins involved in embryonic development

Question 11

what is the purpose of cholesterol in relation to hedgehog

Answer 11

embeds hedgehog in the in the cell membrane

Question 12

what is the role of wingless

Answer 12

switch on expression of hedgehog in the adjacent stripe

Question 13

how are drosophila embryo segments marked out

Answer 13

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

= red and black stripes

Question 14

what is the boundary between the wingless and hedgehog stripes called

Answer 14

the parasegment boundary

Question 15

what does hedgehog do in its segment

Answer 15

induces diffusible wingless in the adjacent cell

Question 16

what happens if hedgehog lacks cholesterol

Answer 16

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

Question 17

describe the hedgehog receptor

Answer 17

patches

= 12 transmembrane domain

Question 18

how does patched work

Answer 18

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

Question 19

what happens in the absence of hedgehog (Hh)

Answer 19

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

Question 20

what happens in the presence of hedgehog (Hh)

Answer 20

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

Question 21

what does the nervous system form from

Answer 21

ectoderm

- overlying the notochord

Question 22

what secretes sonic hedgehog (Shh)

Answer 22

the notochord

Question 23

what does Shh induce

Answer 23

the floor plate which secretes further Shh

Question 24

at high concentrations of Shh, what is specified

Answer 24

motoneurons

Question 25

what is specified at medium Shh conc

Answer 25

V2 interneurons

Question 26

what is specified at low Shh conc

Answer 26

V1 interneurons

Question 27

how can Hh signalling lead to cancer name a specific cancer

Answer 27

Hh stimulates stem cell proliferation in the basal layer of skin excess Hh leads to over proliferation = basal cell carcinoma

Question 28

name a tumour suppressor that acts against Hh

Answer 28

Ptc1

Question 29

how does Ptc1 inhibit Hh

Answer 29

inhibits Hh signalling

Question 30

who is particularly vulnerable to Basal cell carcinoma, why?

Answer 30

Gorlin's syndrome | - they have mutated patched receptors

Question 31

what could be a potential therapeutic avenue for treating some cancers

Answer 31

anti-cancer drugs based on molecules that inhibit Hh signalling

Question 32

what are Wnt proteins involved in (2)

Answer 32

cell cycle regulation | immune cell maintenance

Question 33

what is the name Wnt an amalgamation off

Answer 33

wingless (segment polarity gene) | Int (mouse gene)

Question 34

how many types of Wnt in: humans drosophila

Answer 34

11-12 1

Question 35

describe the structure of Wnt

Answer 35

many cysteines

Question 36

what is the benefit of there being many cysteines in Wnt

Answer 36

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

Question 37

like Hh - Wnt is modified: what modifies Wnt how is it modified

Answer 37

modified by porcupine enzyme fatty acid palmitoleate is added to the conserved serine

Question 38

what are the two receptors for Wnt

Answer 38

LRP | frizzled

Question 39

describe what happens in the absence of Wnt

Answer 39

LRP is not phosphorylated cytoplasmic complex phosphorylates beta-catenin beta-catenin is then targeted for proteosomal degradation TCF represses transcriptional targets

Question 40

describe what happens in the presence of Wnt

Answer 40

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

Question 41

what is the role of wingless

Answer 41

to induce Hh expression in adjacent cells

Question 42

what is an essential function of Wnt

Answer 42

establishing the nieuwkoop centre

Question 43

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

Answer 43

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

Question 44

what can over-expression of Wnt cause

Answer 44

cancer

Question 45

how can Wnt's cause cancer

Answer 45

loss of APCs = excess Wnt signalling prevent beta-catenin degradation = prolonged over expression of genes

Question 46

what mediates the destruction of beta-catenin

Answer 46

APCs

Question 47

what does APC stand for

Answer 47

adenomatous polyposis coli