cellmechs - Overview: the Development of Brain Organization...

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Unformatted text preview: Overview: the Development of Brain Organization • How do axons find their way to their targets? • How do axons recognize and respond to the midline? • How do axons recognize like axons? • How do axons leave a pathway? • How are topographical maps formed? • How are numbers of axons innervating a target matched to target size? • How are synapses formed? • What role does experience play? • How are connections refined? Questions Wiring the Nervous System Overview: the Development of Brain Organization Two classes of factors must be considered: 1. Neurotropins (guidance cues) 2. Neurotrophins (nourishing factors) Overview: the Development of Brain Organization These factors may be: 1. Substrate-bound 2. Diffusible substances Target Location: Where to Start? axon vs. dendrite Target Location: How to Get There contact guidance (substrate-bound) diffusible substances (chemotaxis) galvanotaxis (electrical guidance) timing guideposts How do Growing Axons “Read” These Cues? Growth Cones http://www.abdn.ac.uk/~b A. Guidepost (diffusible or bound) B. Contact guidance (substrate adhesion) C. Chemoaffinity (and chemorepulsion) Contact Guidance Paul Weiss Chemotaxis Rita Levi-Montalcini Victor Hamburger A. Pulled B. Pushed D. Hemmed in contact diffusible Attractant Repellant netrins semaphorins and slits ncams polysialic acid Ligand Receptor Effect Location Netrin Slit Sema EphrinA3 DCC UNC Robo Plexin Ephrins A2, A5 Attract Repel Repel Repel Repel Midline Midline Target Netrin from sanskrit, meaning “to guide” + “in” Semaphorin, from Greek, “sign-bearer” Guidepost Theory Guidepost cells and the pioneer neuron in the developing limb of the grasshopper. O’Connor, T.P. (1999) Intermediate targets and segmental pathfinding. Cellular and Molecular Life Sciences, 55 , 1358-1364. Control of Decussations at the Midline Axon guidance at the cortex midline. Schematic coronal section of a mouse brain at the level of the corpus callosum summarizing known receptors (left) and their ligands. Callosal neurons are guided at the midline by attractive (Netrin, Sema3C) and repulsive (Slit2, Draxin, Wnt5a) proteins secreted by glial cells in the induseum griseum (IG) and glial wedge (GW) and two transient subsets of migrating GABAergic and glutamatergic neurons. How commissural axons switch from attraction to repulsion is unknown. The attractant secreted by GABAergic neurons is also unknown (?). www.sciencedirect. Chédotal, A. (2011) Further tales of the midline. Current Opinion in Neurobiology, 21 , 68-75. Tessier-Levigne, M. & Goodman, C.S. (1996) The molecular biology of axon guidance. Science, 274, 1123-1133. Tessier-Levigne, M. & Goodman, C.S. (1996) The molecular biology of axon guidance. Science, 274, 1123-1133. DCC DCC + Robo DCC+ UNC5 Grunwald, I. & Klein, R. (2002) Axon guidance: Receptor complexes and signaling mechanisms. Current Opinion in Neurobiology, 12, 250-259. Midline crossing in Drosophila mutants “robo” from roundabout Drosophila lacking either slits or robos Tessier-Levigne, M. & Goodman, C.S. (1996) The molecular biology of axon guidance. Science, 274, 1123-1133. Topographical Mapping Marcus Jacobson Roger Sperry Retina Tectum A P C R D V P A C R D V A P C R D V A P D V A P D V Galvanotaxis or Neurobiotaxis (Electrical Guidance) Ross Harrison Neurotrophins...
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This note was uploaded on 11/21/2011 for the course DEP 3053 taught by Professor Miller during the Fall '08 term at University of Florida.

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cellmechs - Overview: the Development of Brain Organization...

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