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How does an axon grow?. Compare the processes of axonal regeneration in peripheral and central nervous system. Relevance. Treatment of disease Neurodegenerative Spinal trauma Scientific puzzle: how so few genes encode such complex structure wiring determines operation

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How does an axon grow?


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how does an axon grow

How does an axon grow?

Compare the processes of axonal regeneration in peripheral and central nervous system.

relevance
Relevance
  • Treatment of disease
    • Neurodegenerative
    • Spinal trauma
  • Scientific
    • puzzle: how so few genes encode such complex structure
    • wiring determines operation
    • ? axonal refashioning & memory formation
how connections achieved
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
growth cone mechanisms
Growth cone mechanisms
  • Filopodia, lamellipodia
  • Actin polymerisation
    • ABPs, Ca / P
  • Vesicle fusion
  • Matrix anchoring
  • Protease secretion
diffusible factors
Diffusible factors
  • NGF
    • Tyrosine kinase (trk)
  • netrin
    • commissure formation
  • Semaphorin

Chemoattractant

Chemorepellant

cellular molecules
N-Cadherin

Ca-dependent

Ig superfamily

N-CAM

NgCAM

Fasciclin II

TAG-1

transient axonal glycoprotein

Fasciculation

Substrate binding

axon-Schwann cell interaction

Cellular molecules

homophilic

heterophilic

matrix molecules
Fibronectin

Laminin

Tenascin

Integrins

large variety

ab 12x6

Matrix molecules

Glycoproteins:

bind to

molecules
Molecules
  • Ig superfamily
    • N-CAM
    • NgCAM
    • TAG-1 (transient axonal glycoprotein)
  • N-cadherin
  • Matrix - bind to Integrins (ab)
    • laminin
    • fibronectin
    • Tenascin
molecules continued
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)
guidance
Guidance
  • Location of neurone
  • Axon destination neurone
  • Axon position on neurone
not the neurone
Not the neurone
  • but the environment – CNS / PNS
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

Normal response to injury

Prevented by trophic factors

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