17 - Signaling Strength and Input Duration Flashcards
What model system is used to study axonal pathfinding?
Xenopus (frog) spinal neuron growth cones
Why was frog spinal neurons chosen as the model system to study axonal pathfinding?
These neurons are very easy to grow (since frogs develop in a live habitat)
What is needed to study axonal pathfinding in the lab?
Prolonged imaging of live cells
What do neurons need to grow in the lab?
Very specific conditions (temperature, humidity, etc.)
True or false: most neurons are easy to culture in the lab
False: they are usually very difficult to grow
Why are most neurons difficult to culture in the lab?
They require very specific conditions
How does a growth cone respond to a positive cue?
It grows towards an increasing concentration
How does a growth cone respond to a negative cue?
It grows away from the increasing concentration
What type of chemoattractant is netrin?
Mainly an axon attractant
True or false: netrin is only a chemoattractant
False: it can also be a chemorepellent rarely
When is netrin a chemorepellant?
When it binds to the UNC5 receptor in C. elegans
In which organism is netrin a chemorepellant?
C. elegans
What receptor does netrin bind to?
DCC and UNC5
What happens when netrin binds to DCC?
It acts as a chemoattractant
What happens when netrin binds o UNC5?
It acts as a chemorepellent
What is DCC?
The receptor for netrin (for attraction)
What is UNC5?
The receptor for netrin (for repulsion)
What type of molecule is netrin?
A secreted protein
What type of chemoattractant is slit?
An axon repellant
What is the receptor for slit?
Robo
What is Robo?
The receptor for slit
What does Robo stand for?
Roundabout
What type of molecule is robo?
A secreted protein
What type of chemoattractant is ephrin?
Mostly repulsion
What type of molecule is ephrin?
Cell surface proteins
What is the receptor for ephrin?
Eph receptors
What do eph receptors do?
Bind to ephrin
What is meant by “bi-directional signaling”?
When the ligand binds to the receptor, both cells (the one expressing the receptor, and the one expressing the ligand) can cause intracellular signaling
Which axon guidance molecule exhibits bi-directional signaling?
Ephrins
What type of chemoattractant is semaphorin?
An axon repellant, and a dendritic attractant
What is semaphorin3A?
A molecular cue important for axonal and dendritic pathfinding
Which molecular cue is a dendritic attractant?
Semaphorin3A
What receptors do semaphorins bind to?
Plexins and neuropilins
What are plexins?
The receptors for semaphorins
What are neuropilins?
The receptors for semaphorins
True or false: semaphorin is only important in dendritic pathfinding
False: it is also a chemorepellent for axonal pathfinding
How does semaphorin interact with its receptors?
The receptors act as a dimer (neuropilins and plexins)
True or false: the body is bilateral
True: we have two similar hemispheres
What separates the brain bilaterally?
The midline
What are commissural axons?
Axons that start it one hemisphere, and cross the midline into the other hemisphere
Which axons have been used to study axonal pathfinding?
Commissural axons
Where are commissural axons found?
Mostly in the spinal cord, but also in the brain
What is the behavior of commissural axons (in terms of the midline)?
First they are attracted to the midline, then they are sharply repelled from the midline
What is present at the midline?
High concentrations of positive and negative cues
What is the problem with the midline?
The axon needs to ignore the negative cues as it approaches it, and ignore the positive cues as it leaves it
What is needed for an axon to cross the midline?
A shift in responsiveness
As the axon approaches the midline, what is it responsive to?
Positive cues (and not negative cues)
As the axon leaves the midline, what is it responsive to?
Negative cues (and not positive cues)
What happens if an axon does not lose responsiveness to positive cues at the midline?
It will stay there and loop around
What model systems were used to study axon midline pathfinding?
- The embryonic ventral nerve cord of fruit flies
2. The embryonic spinal cord of mice and chickens
What mediates the axon moving towards the midline?
Netrin and DCC interactions
What mediates the axon moving away from the midline?
Slit and Robo interactions
What receptors are found in an axon moving towards the midline (in flies)?
DCC
What receptors are found in an axon moving away from the midline (in flies)?
Robo
What is the relationship between Robo and DCC in flies?
A negative crosstalk
What is the mechanism for switching responsiveness to the midline in flies?
The protein commissureless
What is Comm short for?
Commissureless
What does Comm do?
Keeps Robo in intracellular compartments (not on cell surface)
When is Comm expressed?
When the axon is moving towards the midline (in flies)
When is Comm downregulated?
When the axon crosses the midline (in flies)
What is similar between midline crossing in mice and flies?
They both have DCC and netrin attraction
What is different between midline crossing in mice and flies?
Flies have Comm, while mice have Rig-1
Which receptors are found on the axon before crossing the midline (in mice)?
Rig-1 and DCC (with Robo-1 being inhibited)
What does Rig-1 do?
Responds to slit, and inhibits Robo-1
What is another name for Rig-1?
Robo-3
What is another name for Robo-3?
Rig-1
What Robo receptors are found on mice?
Robo-1 and Rig-1
What organism expresses Comm?
Flies
What does Rig-1 bind to?
Slit
What does slit bind to (in mice)?
Rig-1 and Robo-1
What inhibits Robo-1 (in mice)?
Rig-1
What receptors are found on the axon after crossing the midline (in mice)?
Robo-1
What does Robo-1 do to DCC (in mice)?
Inhibit it (prevent attraction)
What is the phenotype of wild type axons at the midline (in flies)
Crossing (sharp as an arrow, then sharp turn)
What is the phenotype of axons at the midline in the absence of slit (in flies)?
Stalling and crossing back
Why do axons have stalling and crossing back if there is no slit?
They constantly are attracted to the netrin at the midline
Would upregulation of Robo-1 in the absence of slit restore the wildtype phenotype?
No, because Robo-1 needs slit to activate its repulsive nature
Why is Robo-1 called “roundabout”?
Because when it is downregulated, the axons loop around the midline
What happens to the phenotype of the axons in the absence of netrin?
Nothing
What is the conclusion about netrin based on deletion studies?
There is redundancy present (other attractants exist)
What happens in axons if Rig-1 is downregulated?
The neurons will not reach the neuron
How come downregulation of Rig-1 causes axons to not reach the midline?
Robo-1 is not inhibited, thus it responds to slit and gets repelled from the midline
How many axons cross the midline?
Millions