Axon Guidance Flashcards
what is the connectome
how nerve cells connect together
when does axon guidance occur
during development of the embryo and shortly after birth
why is identifying genes involved in nerve growth beneficial
aids nerve regrowth in spinal injury and nerve degeneration
limitations of axon guidance
-brain contains 10^11 neurons, each form single/multiple connections
-specificity of connections
-distance of connections
-lack of coding information (only 30-40,000 genes)
scale issues
axon distance is 250x cell body diameter
growth cone function
sensor and motor for growth
axons involved in initial outgrowth
pioneer axons - use a variety of cues to find their specific pathway
developing axons - use scaffold laid out by pioneers (follower axons) select pathways and join via selective fasciculations
guidepost cells/intermediate target cells
division of longer axon pathways into shorter trajectories
what occurs in guidepost cell ablation in grasshoppers
no directionality
what are cues provided by
substrate along they grow
secreted from targets
4 mechanisms to guide axonal outgrowth
contact mediated attraction
contact mediated repulsion/inhibition
chemoattraction
chemorepulsion
axon pathways at midline of SC
motor neurons (axons to periphery)
nerve cells (ipsilateral)
reach target then extend
commissure axons which turn
Unc-6 role and mutant
Grow towards and away from the midline
Dorsal and ventral axon projections impaired
Unc 5 role and mutants
Grow away from midline
Dorsal projections impaired
Unc40 role and mutant
Grow towards midline
Ventral projections impaired
Role of floor plate cells
Located at ventral SC
Attract commissural axons from distance of around 100um
Which unc is netrin similar to in conservation
Unc6
Netrin KO
Commissural axons fail to cross at the midline. Some still cross and orient towards midline
Conservation of netrin receptors
DCC (vertebrates)
Unc-40 (C.elegans)
Frazzled (flies)
What does unc5 bind to
Unc40 and netrin
Converts netrin signal to become a repellant
What is the other attractant the floorplate produces
Shh
what does the roofplate release
BMP7 (repellant)
what is slit
repellant which prevents ipsilateral neurons moving towards the midline
ligand for roundabout
expressed in floorplate
commissureless and roundabout mutants
commissureless mutant - no axons crossing midline
robo mutant - many axons cross and recross
how many slit genes do mice have
3
where is robo protein restricted to
longitudinal regions of commissural axons
all neurons have robo mRNA
where is comm expressed
commissural region of commissural axons
negative regulator of robo
robo and comm transport
robo and comm interact with DNedd4
move to endosome/proteasome
what do robo vary in
cytoplasmic domain and function
role of robo3/rig1
acts like commissureless to control midline crossing
where do commissural axons extend after crossing the midline
anteriorly
via non diffusable cue
what causes anterior extention
wnt4
which molecule prevents posterior crossing
Shh
Shh receptors
cyclopamine insensitive and no SMO receptor involved
alternative Shh receptor Hib used by commissural axons after crossing
role of robo in flies
influences how far axons extend from midline
role of robo in drosophila
robo 1 and 2 prevents axons crossing midline
axon tract positioning (fascicles)
overlapping expression patterns
robo code
place axons a certain distance from midline where they choose which fascicle to join
re-use of fascicle marker
