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Axon guidance, regeneration and brain formation

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Axon guidance, regeneration and brain formation

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    1. Axon guidance, regeneration and brain formation Thomas Kidd Biology Department http://www.unr.edu/biology/kidd.htm

    3. What don’t spinal injuries heal?

    4. The Central Nervous System: the body’s controller

    5. 100 billion neurons in the human brain Number of connections is guessed at 1015

    9. Growth of pioneer tracts in the mouse brain

    10. Brain wiring and Bilateral Symmetry

    11. Human Horizontal Gaze Palsy Patient

    12. Growth Cone Model

    13. The Growth Cone

    16. Why don’t CNS axons regenerate?

    17. How do we study normal axon growth? Find a simplified system mice or fruit flies Biochemical approach Purification of the Netrin chemoattractant Genetic approach Identification of the Slit chemorepellent

    18.

    20. Commissural axon assay system The commissural axons are a simplified system They respond to the floor plate chemoattractant Can test protein fractions for activity We know there is a chemoattractant made by the floor plate Tessier-Lavigne et al. extracted and ground up 25,000 chick embryo spinal cords Biochemically fractionated the extracts and tested them on commissural axons Found a protein responsible and called it Netrin-1

    21. Netrin is made the floor plate

    22. Netrin-1 mutant mouse

    23. Netrin is the chemoattractant for commissural axons

    24. Netrin-1 is a chemoattractant Netrin-1 was biochemically purified from chick spinal cords As an activity which causes commissural axons to grow Netrin-1 attracts developing axons Netrin-1 is a chemoattractant Genetic mutants prove Netrin-1 is required in vivo

    25. Fruit Fly Embryo Nervous System

    26. Drosophila Embryonic Central Nervous System

    27. Genetic screens identify axon guidance mutants in Drosophila

    28. In slit mutants, the axons never leave the midline of the CNS

    29. Slit is made at the midline

    30. Conservation of Function

    32. Human Horizontal Gaze Palsy Patient

    33. Axon Guidance Summary Understanding the cues that guide developing axons May help us to design therapies for spinal cord repair Will help us understand how the brain develops Chemoattractants attract growing axons Netrin-1 was identified biochemically as a chemoattractant Could be used to stimulate axon growth Chemorepellents repel growing axon Slit was identified genetically as a chemorepellent Inhibit Slit/Robo signaling to allow axon growth Want more information? Links on Kidd laboratory website http://www.unr.edu/biology/kidd.htm

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