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How does an axon grow? Compare the processes of axonal regeneration in peripheral and central nervous system. Dr Sanjay Manohar University of Oxford http://www.smanohar.com.

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Presentation on theme: "How does an axon grow? Compare the processes of axonal regeneration in peripheral and central nervous system. Dr Sanjay Manohar University of Oxford http://www.smanohar.com."— Presentation transcript:

1 How does an axon grow? Compare the processes of axonal regeneration in peripheral and central nervous system. Dr Sanjay Manohar University of Oxford

2 Relevance Treatment of disease Scientific Neurodegenerative
Spinal trauma Scientific puzzle: how so few genes encode such complex structure wiring determines operation ? axonal refashioning & memory formation

3 Axon Growth

4 How connections achieved
Prespecification Random connections Target induced specification endplate formation, postsynaptic terminals Death of incorrectly wired neurones Motor neurones (Levi-Montalcini) Pruning of synapses & arbors muscle fibres

5 Neural crest

6 Growth cone mechanisms
Filopodia, lamellipodia Actin polymerisation ABPs, Ca / P Vesicle fusion Matrix anchoring Protease secretion

7 Sperry & Stone

8 Control of growth

9 Diffusible factors NGF netrin Semaphorin Tyrosine kinase (trk)
commissure formation Semaphorin Chemoattractant Chemorepellant

10 Cellular molecules N-Cadherin Ig superfamily Fasciculation
Ca-dependent Ig superfamily N-CAM NgCAM Fasciclin II TAG-1 transient axonal glycoprotein homophilic Fasciculation Substrate binding axon-Schwann cell interaction heterophilic

11 Matrix molecules Fibronectin Laminin Tenascin Integrins large variety
Glycoproteins: bind to Fibronectin Laminin Tenascin Integrins large variety ab 12x6

12 Molecules Ig superfamily N-cadherin Matrix - bind to Integrins (ab)
N-CAM NgCAM TAG-1 (transient axonal glycoprotein) N-cadherin Matrix - bind to Integrins (ab) laminin fibronectin Tenascin

13 Molecules (continued)
Trophic (prevent death) Neurotrophins NGF via retrograde transport to soma induces NA synthesis required during a critical period BDNF (in DRG) sphingolipids eg. Ceramide Chemotactic NGF via Tyr K (trk)

14 Guidance Location of neurone Axon destination neurone
Axon position on neurone

15 Regeneration

16 Spectrum of ability

17 Not the neurone but the environment – CNS / PNS

18 Normal response to injury
PNS distal segment degeneration (phagocytes) Schwann cell didifferentiation proximal segment axon regrowth CNS distal segment degeneration (microglia) oligos proliferate proximal segment degenerates cell body may die Prevented by trophic factors

19 Inhibition of regrowth
Nogo (Schwab, 1985) Myelin associated glycoprotein (MAG)

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