Week 7 Flashcards
What is contact guidance in axon pathfinding?
What are some forms of contact guidance?
- When the growth cone responds to CELL-SURFACE cues
- Guidepost cells: act as intermediate targets for axons
- Axons (with the exception of pioneer axons) can bind and unbind from other neurons that are going the same way via fasciculation and defasciculation
What is fasciculation? How do neurons undergo selective fasciculation? and how do neurons defasciculate?
What proteins are involved
- A process by which axons become bundled together, forming a fascicle
- Selectivity is due to the growth cone being able to distinguish among and extend along specific axonal surfaces via the use of cell surface proteins such as cadherins, fascicilin (Fas), and neuroglian (L1) and homophilic adhesion. This is how fascicles can run perpendicular to eachother in the drosophila ventral nerve cord
- Neurons defasciculate via BEATEN PATH, a secreted protein that locally disrupts fasciclin homophilic interaction
Pioneer axons can not really use fasciculation for obvious reasons. How do they navigate?
Chemotropism
What is Netrin? From where is it expressed?
- A morphogenic chemotactic cue expressed in the VENTRAL midline used for commissural neurons
Netrin is used to guide axons in the neural tube. How does it work in this setting?
Netrin is released from the floor plate of the neural tube that is used to guide commissural neurons from the dorsal end of the neural tube to the ventral end
What is the netrin homologue in c.elegans?
And what are the
a) Attractive receptors
b) Repellant receptors
UNC-6
a) UNC40
b) UNC5
Axons need to cross the floor plate, so they don’t actually stop at the highest concentration of netrin.
How do they do this?
What are the 2 attractive and 4 repellant netrin receptors in mammals?
Attractive
- DCC
- Neogenin
Repellant
- UNC5H1
- UNC5H2
- UNC5H3
- UNC5H4
What is the most common fluorescent dye used to observe axon guidance?
DiI (dye-eye)
- Can be used anterograde: labelling the cell body, identifies where the axon is going
- Or retrograde: identifies which neurons innervate what area
How do commissural neurons react to an ectopic floor plate when it is:
a) before the midline
b) after the midline
Why?
a) Attracted to the floor plate
b) Not attracted
This is because after the neurons have crossed the floor plate, they turn off their sensitivity to netrin
What is the role of SLIT in drosophila?
- Slit encodes a midline repellant signal
- Slit mutants: commissural axons still attracted to midline glia but get stuck there
What is the function of the ROBO family in drosophila?
- Encodes receptors for slit
- ROBO 1, 2 and 3 are receptors for the midline repellant slit
- ROBO-1 mutants cross the midline inappropriately and repeatedly
- ROBO triple mutants resemble slit mutants
What is the role of COMM in drosophila?
- Comm grows along netrin gradient to midline
- Prevents ROBO reaching growth cone (therefore keeps axon on netrin gradient)
- Reaching midline, Comm is downregulated, allowing ROBO to become active
- Slit received and midline is repelled
In vertebrates, the pathway is not the exact same. Vertebrates have homologues of ROBO and Slit, but not Comm.
What is the mechanism that replaces Comm in vertebrates?
Comm function is mediated by the Nedd4 E3 ubiquitin ligase pathway.
This degrades ROBO in pre-crossing axons and prevents ROBO breakdown post-crossing
What do axons do after crossing the midline? What do they then respond to?
- After crossing the midline, vertebrate commissural axons turn toward an anterior source of Wnt4
