AXON GUIDANCE Flashcards
What are the two theories explaining how specific neuronal connections arise in the nervous system?
1.Weiss-resonance theory
random and diffuse neuronal outgrowth
2.Sperry- chemoaffinity hypothesis
direct and specific outgrowth occurs
What kind of axon growth is seen in embryos- and which theory does it prove?
Highly organised, reproducible and stereotyped axon outgrowth
SPERRY
What evidence supported the idea of guidance cues
Reverse segment of the neural tube in chick embryo
result=
T7 and L1 motor axons still innervate normal muscle targets
What are guidance cues?
Factors in the environment that axons can use to find their correct targets
What did experiments on grasshoppers conclude?
Labelled- pathway hypothesis
Guidance cues are found on axons
Tested by ablating cells that might carry potential cues and seeing the effects on nearby axons
Example of an axon scaffold in vertebrates
The subplate neurons in the mammalian cortex create an axon scaffold- which LGN neurons then use in order to innervate the cortex
In developing embryos- where can guidance cues be found?
- In the boundaries of domains of patterning gene expression
- Boundaries of rhombomeres
- Boundaries of the floor plate
What are the four forces of axon guidance?
Contact attraction
Chemoattraction
Contact repulsion
Chemorepulsion
What are lamella and filopodia?
Two components of the growth cone
Filopodia (extensions)- actin bundles polarised to form larger bundles
Lamella- actin bundles cross linked into a net
What occurs when the growth cone encounters an attractive cue
- Rearward actin treadmilling slows- forward movement of the filopodium
- Microtubules are pulled into the extending filopodium
What is a permissive structure?
Substrates which allow growth cones to grow- do not direct movement
What is laminin?
Permissive structure
Growth promoting xtra cellular protein
permissive but not instructive
What are non-permissive structures- what can they still do
Contact repellants-
can still channel axon growth
What are 2 examples of contact repellants
Semaphorins- secreted and membrane bound forms cause growth cone collapse Ephrins- early: compartmentalise the embryo into discrete domains later:keep axons out of specific areas
An example of a chemoattractant
Netrin-floorplate protein
An example of a chemorepellant
BMP- roofplate protein
Which proteins are involved in changing growth cone sensitivites
Robo- Slit
COMM
How do the levels of Robo and Comm change in an axon before and after it crosses the floor plate midline?
Robo expressed in high levels after commissural axons cross the midline
Comm expressed in high levels b4 midline (encodes a trafficking protein)
How do axons’ sensitivity change to netrins in the floor plate after the midline is crossed?
Sensitivity is decreased
How do axons stay on the axon scaffold
Fasciculation to the scaffold-
homophillic binding to CAMs on the scaffold
When do axons know when to leave the scaffold?
- Address labels- specific target molecules
e. g Netrin- chemoattractant expressed in specific muscles - Gradients of ephrins (retinotectal system)- topographic maps
What evidence is there for gradients of ephrins (repels temporal retinal axons) in the posterior tectum
- The activity is abolished by heat treatment of posterior but not anterior membranes
- Posterior membranes cause temporal growth cones to collapse in vitro
What do Fas 2 mutants have?
Many defasciculated axons in ventral cord longitudinal tracts
What does over expression of Fas 2 cause?
‘By-pass phenotype’
Motor axons fail to desfaciculate- miss their targets
