Diffusible molecular cues and cell surface cues guide axon growth

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Diffusible molecular cues and cell surface cues guide axon growth
Repulsive cues guide DRG & olfactory axons to their targets
Growth cones collapse after contact with repulsive axonal factor
Semaphorins (“Collapsins”): ligands for neuropilins & plexins
Ti1 pioneer neurons need Cx1 cells or net repulsion blocks
outgrowth
The Cx1 processes have chemoattractants to guide Ti1 neuron
outgrowth
The spinothalamic pain pathway: C fibers to 2nd order projection
neurons to brain
Spinothalamic tract=
main pain pathway
stem & thalamus
Motor neurons are in the ventral horn, & sensory neurons are in
the dorsal horn of the spinal cord
DRG neurons project to 3 functional domains of the spinal cord:
motor & pain areas
DRGs form dense projections in culture + NGF
DRG outgrowth is repelled by Sema3A-expressing cells
NGF is a potent long-range chemoattractant
How do the spinothalamic neurons know where to go?
Dorsal spinal neurons grow ventrally toward floor plate at midline
Commissural neurons are attracted to Netrin-1 in floorplate
Both vertebrate and invertebrate sensory neurons grow toward
netrin/UNC-6
Trochlear (eye) motor neurons project away from Netrin
Genetic experiments in C. elegans identified key regulators in
axon guidance (SNs & MNs)
UNC-5 &
UNC-40:
receptors
For UNC-6
Sensory neurons: UNC-40+. Motor neurons: UNC-5; UNC-40+
Unc-5 receptor causes motor neurons to be repelled by Netrin
Direction
of outgrowth
Netrins share similarity with laminin γ subunits in the ECM
Slit chemorepellant coexpressed with netrin in the ventral midline
Robo: Slit
receptor
DCC: Netrin
receptor
Midline commissural mutants in Drosophila reveal crossing
mechanism
Midline 
(high Slit)
Comm degrades Robo
to cross midline, then
leaves Robo intact
(degrades Robo;
Robo persists &
repels from midline
in mutants)
(Slit ligand; no
midline repulsion in
Robo mutants)
Commissural axons: balancing repulsion (Slit) and attraction
(Netrin)
Conserved mechanism of midline crossing in flies and vertebrates
Rig 1
Many types of guidance cues for axons
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