17 - Signaling Strength and Input Duration Flashcards

1
Q

What model system is used to study axonal pathfinding?

A

Xenopus (frog) spinal neuron growth cones

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2
Q

Why was frog spinal neurons chosen as the model system to study axonal pathfinding?

A

These neurons are very easy to grow (since frogs develop in a live habitat)

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3
Q

What is needed to study axonal pathfinding in the lab?

A

Prolonged imaging of live cells

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4
Q

What do neurons need to grow in the lab?

A

Very specific conditions (temperature, humidity, etc.)

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5
Q

True or false: most neurons are easy to culture in the lab

A

False: they are usually very difficult to grow

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6
Q

Why are most neurons difficult to culture in the lab?

A

They require very specific conditions

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7
Q

How does a growth cone respond to a positive cue?

A

It grows towards an increasing concentration

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8
Q

How does a growth cone respond to a negative cue?

A

It grows away from the increasing concentration

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9
Q

What type of chemoattractant is netrin?

A

Mainly an axon attractant

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10
Q

True or false: netrin is only a chemoattractant

A

False: it can also be a chemorepellent rarely

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11
Q

When is netrin a chemorepellant?

A

When it binds to the UNC5 receptor in C. elegans

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12
Q

In which organism is netrin a chemorepellant?

A

C. elegans

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13
Q

What receptor does netrin bind to?

A

DCC and UNC5

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14
Q

What happens when netrin binds to DCC?

A

It acts as a chemoattractant

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15
Q

What happens when netrin binds o UNC5?

A

It acts as a chemorepellent

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16
Q

What is DCC?

A

The receptor for netrin (for attraction)

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17
Q

What is UNC5?

A

The receptor for netrin (for repulsion)

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18
Q

What type of molecule is netrin?

A

A secreted protein

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19
Q

What type of chemoattractant is slit?

A

An axon repellant

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20
Q

What is the receptor for slit?

A

Robo

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21
Q

What is Robo?

A

The receptor for slit

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22
Q

What does Robo stand for?

A

Roundabout

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23
Q

What type of molecule is robo?

A

A secreted protein

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24
Q

What type of chemoattractant is ephrin?

A

Mostly repulsion

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25
Q

What type of molecule is ephrin?

A

Cell surface proteins

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26
Q

What is the receptor for ephrin?

A

Eph receptors

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27
Q

What do eph receptors do?

A

Bind to ephrin

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28
Q

What is meant by “bi-directional signaling”?

A

When the ligand binds to the receptor, both cells (the one expressing the receptor, and the one expressing the ligand) can cause intracellular signaling

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29
Q

Which axon guidance molecule exhibits bi-directional signaling?

A

Ephrins

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30
Q

What type of chemoattractant is semaphorin?

A

An axon repellant, and a dendritic attractant

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31
Q

What is semaphorin3A?

A

A molecular cue important for axonal and dendritic pathfinding

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32
Q

Which molecular cue is a dendritic attractant?

A

Semaphorin3A

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33
Q

What receptors do semaphorins bind to?

A

Plexins and neuropilins

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34
Q

What are plexins?

A

The receptors for semaphorins

35
Q

What are neuropilins?

A

The receptors for semaphorins

36
Q

True or false: semaphorin is only important in dendritic pathfinding

A

False: it is also a chemorepellent for axonal pathfinding

37
Q

How does semaphorin interact with its receptors?

A

The receptors act as a dimer (neuropilins and plexins)

38
Q

True or false: the body is bilateral

A

True: we have two similar hemispheres

39
Q

What separates the brain bilaterally?

A

The midline

40
Q

What are commissural axons?

A

Axons that start it one hemisphere, and cross the midline into the other hemisphere

41
Q

Which axons have been used to study axonal pathfinding?

A

Commissural axons

42
Q

Where are commissural axons found?

A

Mostly in the spinal cord, but also in the brain

43
Q

What is the behavior of commissural axons (in terms of the midline)?

A

First they are attracted to the midline, then they are sharply repelled from the midline

44
Q

What is present at the midline?

A

High concentrations of positive and negative cues

45
Q

What is the problem with the midline?

A

The axon needs to ignore the negative cues as it approaches it, and ignore the positive cues as it leaves it

46
Q

What is needed for an axon to cross the midline?

A

A shift in responsiveness

47
Q

As the axon approaches the midline, what is it responsive to?

A

Positive cues (and not negative cues)

48
Q

As the axon leaves the midline, what is it responsive to?

A

Negative cues (and not positive cues)

49
Q

What happens if an axon does not lose responsiveness to positive cues at the midline?

A

It will stay there and loop around

50
Q

What model systems were used to study axon midline pathfinding?

A
  1. The embryonic ventral nerve cord of fruit flies

2. The embryonic spinal cord of mice and chickens

51
Q

What mediates the axon moving towards the midline?

A

Netrin and DCC interactions

52
Q

What mediates the axon moving away from the midline?

A

Slit and Robo interactions

53
Q

What receptors are found in an axon moving towards the midline (in flies)?

A

DCC

54
Q

What receptors are found in an axon moving away from the midline (in flies)?

A

Robo

55
Q

What is the relationship between Robo and DCC in flies?

A

A negative crosstalk

56
Q

What is the mechanism for switching responsiveness to the midline in flies?

A

The protein commissureless

57
Q

What is Comm short for?

A

Commissureless

58
Q

What does Comm do?

A

Keeps Robo in intracellular compartments (not on cell surface)

59
Q

When is Comm expressed?

A

When the axon is moving towards the midline (in flies)

60
Q

When is Comm downregulated?

A

When the axon crosses the midline (in flies)

61
Q

What is similar between midline crossing in mice and flies?

A

They both have DCC and netrin attraction

62
Q

What is different between midline crossing in mice and flies?

A

Flies have Comm, while mice have Rig-1

63
Q

Which receptors are found on the axon before crossing the midline (in mice)?

A

Rig-1 and DCC (with Robo-1 being inhibited)

64
Q

What does Rig-1 do?

A

Responds to slit, and inhibits Robo-1

65
Q

What is another name for Rig-1?

A

Robo-3

66
Q

What is another name for Robo-3?

A

Rig-1

67
Q

What Robo receptors are found on mice?

A

Robo-1 and Rig-1

68
Q

What organism expresses Comm?

A

Flies

69
Q

What does Rig-1 bind to?

A

Slit

70
Q

What does slit bind to (in mice)?

A

Rig-1 and Robo-1

71
Q

What inhibits Robo-1 (in mice)?

A

Rig-1

72
Q

What receptors are found on the axon after crossing the midline (in mice)?

A

Robo-1

73
Q

What does Robo-1 do to DCC (in mice)?

A

Inhibit it (prevent attraction)

74
Q

What is the phenotype of wild type axons at the midline (in flies)

A

Crossing (sharp as an arrow, then sharp turn)

75
Q

What is the phenotype of axons at the midline in the absence of slit (in flies)?

A

Stalling and crossing back

76
Q

Why do axons have stalling and crossing back if there is no slit?

A

They constantly are attracted to the netrin at the midline

77
Q

Would upregulation of Robo-1 in the absence of slit restore the wildtype phenotype?

A

No, because Robo-1 needs slit to activate its repulsive nature

78
Q

Why is Robo-1 called “roundabout”?

A

Because when it is downregulated, the axons loop around the midline

79
Q

What happens to the phenotype of the axons in the absence of netrin?

A

Nothing

80
Q

What is the conclusion about netrin based on deletion studies?

A

There is redundancy present (other attractants exist)

81
Q

What happens in axons if Rig-1 is downregulated?

A

The neurons will not reach the neuron

82
Q

How come downregulation of Rig-1 causes axons to not reach the midline?

A

Robo-1 is not inhibited, thus it responds to slit and gets repelled from the midline

83
Q

How many axons cross the midline?

A

Millions