Axon Guidance Molecules - Ephrins Flashcards
What are the 2 classes of Ephrins and how many receptors and Ligands are in each class?
- 10 Eph A R
- 6 Eph B R
- 6 Ephrin A ligands
- 3 Ephrin B ligands
(Eph A’s preferentially bind to Ephrin A ligands & the same with the B class)
What is Eph A signalling linked to?
Repulsion if growing axons. It’s unidirectional
What is Eph B linked to?
Eph B signalling is implicated in bidirectional signalling between the growth come and its surrounding environment.
(Both the cells expressing ligand and receptor can respond to signals. Eph-R produces the forward signal and the Ephrin ligand produces the reverse signal)
What mediates bidirectional signalling in Ephrin B ligands?
An intercellular domain that possess kinase activity. This allows the ligands to act as R’s once bound to the actual Eph B R.
This the downstream signalling cascade occurs in both cells
What are Ephrins called in Drosophila?
Dephrins
Where is Dephrin & DEph R expressed?
Dephrin:
In the cell bodies of most neutron and at the lateral border of the CNS
DEph R:
On axons if longitudinal and commissural interneurons
What happens when Dephrin signalling is messed with?
Bossing & Brand (2002) found that if they expressed Dephrin at the midline where commissural axons usually cross. The commissural axons don’t grow and fail to cross the midline.
They know DEph R are expressed on commissural axons.
This is how they found Dephrin-DEph signalling is repulsive.
What is the Dephrin expressed at the lateral border of the CNS useful for?
Ensuring Dephrin does not stray out of the nervous system
How did Bossing & Brand (2002) find that Dephrin @ the lateral border prevents longitudinal axons leaving the nervous system?
They looked at the ipsilateral neurons (MP2 & MP1) and stained them.
They saw that:
- the cell body is located medially but the axon grew out laterally towards the edge of the CNS & then turns to project longitudinally.
When Dephrin signalling is perturbed there are defects in the growth of these neurons
What happens to longitudinal axons when Dephrin signalling is knocked down?
The MP2 neurons turn to exit the CNS and enter the periphery instead of turning to travel longitudinally.
What has been suggested why motor neurons can leave the CNS but longitudinal axons cannot?
Most neurons in Drosophila larvae express DEph R, but motor neurons do not.
It is possible they can exit the CNS because they are not repelled by the Dephrin @ the border.
How does Dephrin/DEph knockdown cause defects in commissural axons?
- Dephrins are expressed in the midline cells that are adjacent to where commissural axons cross & DEph is expressed in the commissural axon
- Therefore, these Dephrin-DEph signalling provides repulsive cues that keep the commissures separate
- Thus, the loss of Dephrin/DEph will lead to fusion of the commissures
What is the 2 suggested roles of contact Dephrin signalling ?
1) Ensure certain neurons do not stray out of the CNS
2) Ensure commissural axons cross in tight fascicles along the nerve cord
What can negatively affect the roles of Dephrin contact signalling?
- Knockinh down DEph R on growth cones
* knocking down Dephrin expression in cells (lateral border & between commissural crossing)
Where do corticospinal axons originate from and travel to?
Original from: Motor cortex
Travel to: spinal cord motor neurons
