Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BMS381 Developmental Neurobiology > L4 - Reprogramming > Flashcards

L4 - Reprogramming Flashcards

1
Q

Axons reprogram when they reach

A

Choice points

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens to C-axons once they have crossed the floorplate

A

NO LONGER RESPOND to netrins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the experiment used to show that once the FP has been crossed C axons no longer respond to netrin

A

Ectopic grafting of the floorplate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What also happens to c-axons once the floor plate has been crossed

A

Become sensitive to repellants as well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the reason why c-axons become sensitive to repellants post crossing of the floor plate

A

Creates channels through which the c-axons can grow through

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Insect midline glial cells express ___________(e.g_________) and ___________(e.g_________)

A 
diffusible attractants (e.g. netrins)
cell surface repellents (e.g. slits)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does robo encode

A

a receptor for the inhibitory slit protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Robo is expressed at high levels on _____

What is the logic behind this

A

Expressed at high levels on axons that DO NOT cross the midline

Robo is the receptor for slit, thus if Robo is high the cell is able to sense lots of the inhibitory slit molecule hence it is repelled from the midline and will not cross

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe how Robo expression on c-axons changes

A

Initially expressed at low levels - once the midline is cross the axons express Robo at high levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the robo mutant

A

No robo = no receptor for slit = no slit detected

Axons go back and forth across the midline forms roundabouts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where is comm expressed (2)

A

Midline cells and axons that normally cross the midline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the effect of lacking Comm

A

Robo protein expressed at high levels in those cells that would normally cross the midline and which extend longitudinally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What happens when Comm expression is forced

A

Robo lost everywhere so no sensitivity to Slit

Roundabout (robo) phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the two models for how comm regulates Robo

A

Sorting

Clearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the sorting model

A

Presence of comm forces sorting of newly synthesised Robo into late endosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the clearance model

A

Homophilic binding of Comm causes clearance of Robo from the cell surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is an attraction to the clearance model

A

It suggests a mechanism for the upregulation of Robo in crossed axon segments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the results of Keleman 2005 expt to ask if Comm is required for midline cells for correct crossing

A

Neuron specific promoter used to drive an axonal marker
Same promoter was used to drive comm expression in comm mutants background

FOUND - rescue is also turned on in midline cells (using a midline specific promoter) - YOU DONT NEED COMM MIDLINE EXPRESSION TO RESCUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is one of the differences between the sorting and clearance model

A

In SORTING Robo should not be shipped down the axon in the presence of Comm whereas it would be if it was cleared at the cell surface (CLEARANCE)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How could you test to see if Robo protein is being transported down the axon

A

Robo-GFP fusion

Results showed Robo-GFP is found in an axon without comm - so robo transports along the axon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the limitations of the sorting model even though it appears to be correct

A

Why comm is on the midline

What controls the upregulation of Robo on the contralateral side

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe how cell surface expression also changes in mammals

A

E.g. TAG-1 and L1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Has a comm homolog been found in mammals

A

No

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is found in mammals in place of comm

A

Another robo-like receptor (Robo3 AKA Rig-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When is Robo3 expressed

A

Pre crossing axons

26
Q

What is the effect of knocking out in mice`

A

Prevents crossing of the floor plate

27
Q

Journal club paper for reprogramming lecture

A

Sabatier et al 2004

28
Q

What did Sabatier et al look to confirm in their paper

A

How Robo3 worked

29
Q

What were the two models from Sabatier et al for how Robo3 works

A

1) Rig-1 is an attractive receptor required for floor plate crossing
2) Rig-1 prevents sensitivity to a floor plate repellent

30
Q

Pre corssing C axons from ROBO3 knockouts are …

A

Prematurely sensitive to slits

31
Q

Attraction to the midline in ROBO3 KOs can be restored if

A

Slit function is blocked

32
Q

What method would be used to restore slit function

A

Using soluble Robo

Soluble Robo binds to Slit in the culture prevetning it binding to Robo on the axons

33
Q

Wild type pre-crossing axons _______ in the presence of netrin

A

Ignores slit

34
Q

SO WHAT IS THE FUNCTION OF ROBO3

A

Prevent premature sensitivity to Slit

35
Q

Role of Robo3 is ________ to the role of Comm in flies

This role is

A

Analogous

Prevents Robo from signalling before the midline which allows netrin to signal via its receptor

36
Q

What is the receptor for netrin

A

DCC

37
Q

What is different between Robo3 in mammals and comm in flies

A

The mechanism

Loss of Robo3 DOES NOT lead to an upregualtion of Robo on pre crossing axons

Losing comm would lead to the upregulation of robo - comm mutant - no axons cross the FP

38
Q

What is thought to now be the effect of Slit binding Robo at the cell surface

A

Resulting signal amplifies Robo expression

39
Q

Robo3 may be required to …

A

Prevent premature slit response as C axons approach the Fp

40
Q

Evidence suggests that at ___________ slit-induced Robo signalling _______ Robo3 inhibition which then ________ robo3 expression __________ robo and _______ slit mediated repulsion

A 
Certain threshold concentration 
Overwhelms Robo3 inhibition 
TUrns off 
Full stabilising 
Activating
41
Q

The effect of turning to netrins is inhibited in what circumstances

A

When slit is present

42
Q

What is the effect of slit on netrin

A

Slit inhibits netrin

43
Q

What are the two models which could explain how Slit inhibits netrin

A

Model 1: Ligand-ligand interaction

Model 2: Receptor-mediated silencing

44
Q

Describe model 1 - ligand ligand interaction

A

slit directly inhibits the netrin ligand

45
Q

Describe model 2 - receptor mediated signalling

A

slit bidning to robo inhibits the compelx formed when netrin binds to DCC

46
Q

What is the only thing that is required to block the response to netrin

A

Robo IC domain

47
Q

How was it shown that it was the IC domain is required to block the response to netrin

A

Express hybrid version version of Robo
E.g. IC domain of Robo and the EC domain of Met (the HGF receptor)

When HGF applied it was seen that the turning response could be blocked
Since normally HGF doesnt could this response - isnt due to ligand but due to receptor interactions

48
Q

So what is the mechanism for slit inhibitiing netrin

A

Silencing of the netrin response by Slit is due to an interaction between the cytoplasmic domains of DCC and Robo

49
Q

BEFORE THE MIDLINE (ROBO3 AND ROBO)

A

Robo3 silences Robo

50
Q

AFTER THE MIDLINE (ROBO AND SLIT)

A

Activation of Robo by slit silences DCC signalling

51
Q

What throws the switch determine if Robo3 silences Robo or activation of Robo by slit silences DCC signalling

A

Contact with the floor plate triggers it

Changes over time in a cell intrinsic manner (essentially a clock)

52
Q

What is the evidence that contact with the floorplate flips the switch

A

Robo story - suggests high conc slits will stabilise robo on cell surface TURNING ON slit senstivity as the FP is crossed

53
Q

How does Sema sensitivity change as the floor plate is crossed

A

Contact mediated by Tag1 and NrCAM (on FP) to stabilise Sema receptors on C axons

54
Q

What is the effect of treating c aoxns with Shh

A

Turns on Sema sensitivity

55
Q

Shh initially also attracts

A

C axons

56
Q

What changes with rgeards to Shh as C axons cross

A

Attraction of c axons to Shh changes to repulsion

57
Q

what is the effect of a Smo KO

A

Confused crossing and turning defects

58
Q

Response of C axons to Shh reversed by …

A

A cell intrinsic increase in 14-3-3 expression

59
Q

How is Wnt4 an important factor for guidance

A

Wnt to Fzd to GSK3B and DVL - DVL affects the par 3 complex

60
Q

14-3-3 is a ______ homolog

What is its function

A

Par 5

Inhibits protein kinase A

BMS381 Developmental Neurobiology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions