Diffusible molecular cues and cell surface cues guide axon growth.

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Presentation transcript:

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

Spinothalamic tract= main pain pathway stem & thalamus The spinothalamic pain pathway: C fibers to 2 nd order projection neurons to brain

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  (high Slit) (degrades Robo; Robo persists & repels from midline in mutants) (Slit ligand; no midline repulsion in Robo mutants) Comm degrades Robo to cross midline, then leaves Robo intact Midline commissural mutants in Drosophila reveal crossing mechanism

Commissural axons: balancing repulsion (Slit) and attraction (Netrin)

Rig 1 Conserved mechanism of midline crossing in flies and vertebrates

Many types of guidance cues for axons