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Published byWilla Morgan Modified over 8 years ago
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Diffusible molecular cues and cell surface cues guide axon growth
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Repulsive cues guide DRG & olfactory axons to their targets
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Growth cones collapse after contact with repulsive axonal factor
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Semaphorins (“Collapsins”): ligands for neuropilins & plexins
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Ti1 pioneer neurons need Cx1 cells or net repulsion blocks outgrowth
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The Cx1 processes have chemoattractants to guide Ti1 neuron outgrowth
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Spinothalamic tract= main pain pathway stem & thalamus The spinothalamic pain pathway: C fibers to 2 nd order projection neurons to brain
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Motor neurons are in the ventral horn, & sensory neurons are in the dorsal horn of the spinal cord
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DRG neurons project to 3 functional domains of the spinal cord: motor & pain areas
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DRGs form dense projections in culture + NGF
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DRG outgrowth is repelled by Sema3A-expressing cells
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NGF is a potent long-range chemoattractant
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How do the spinothalamic neurons know where to go?
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Dorsal spinal neurons grow ventrally toward floor plate at midline
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Commissural neurons are attracted to Netrin-1 in floorplate
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Both vertebrate and invertebrate sensory neurons grow toward netrin/UNC-6
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Trochlear (eye) motor neurons project away from Netrin
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Genetic experiments in C. elegans identified key regulators in axon guidance (SNs & MNs) UNC-5 & UNC-40: receptors For UNC-6
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Sensory neurons: UNC-40+. Motor neurons: UNC-5; UNC-40+
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Unc-5 receptor causes motor neurons to be repelled by Netrin Direction of outgrowth
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Netrins share similarity with laminin γ subunits in the ECM
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Slit chemorepellant coexpressed with netrin in the ventral midline Robo: Slit receptor DCC: Netrin receptor
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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
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Commissural axons: balancing repulsion (Slit) and attraction (Netrin)
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Rig 1 Conserved mechanism of midline crossing in flies and vertebrates
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Many types of guidance cues for axons
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