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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 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
