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Journal of Neurology

, Volume 242, Supplement 1, pp S22–S24 | Cite as

Inhibitory molecules in development and regeneration

  • Jerry Silver
Article

Abstract

In addition to chemotrophic and contact guidance theories that explain how long projection neurons weave intricate patterns of connectivity within developing or regenerating neuronal networks, there has been recent interest in mechanisms that guide axons by actively constraining, inhibiting or repelling axon growth cones. Developmental boundaries are especially important in regions where large numbers of growing axons must change direction in order to remain on course towards their potential targets. Regenerative boundaries can also have severe pathological consequences since they limit the potential for axon regrowth following injury or diseases. Some of the molecular mechanisms that generate repulsive environments in the embryo are re-expressed in the adult following injury. In the developing retina, a chondroitin sulfate-proteoglycan appears to play an essential role in controlling the sequence of ganglion cell differentiation and initial direction of axons. In several lesion models, re-expression of a chondroitin sulfate-proteoglycan by reactive astrocytes limits regeneration through glial scars; conversely, in experiments where boundary molecules have been manipulated by chondroitinase digestion, axons are stimulated to regrow or reroute to inappropriate pathways.

Keywords

Retina Ganglion Cell Growth Cone Neuronal Network Inhibitory Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Brittis PA, Canning DR and Silver J (1992) Chondroitin sulfate as a regulator of neuronal patterning in the retina. Science 255: 733–736Google Scholar
  2. 2.
    Canning DR, McKeon RJ, DeWitt DF, Perry G, Wujek J, Frederickson R and Silver JR (1993) Beta-amyloid of Alzheimer's disease induces reactive gliosis that inhibits axonal outgrowth. Exp. Neurol 124: 289–298Google Scholar
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    McKeon RJ, Schreiber RC, Rudge JS and Silver JR (1991) Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci 11: 3398–3411Google Scholar
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    Pindzola RR, Doller C and Silver JR (1993) Putative inhibitory extracellular matrix molecules at the dorsal root entry zone of the spinal cord during development and after root and sciatic nerve lesions. Dev Biol 156: 34–48Google Scholar
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    Silver JR, Edwards M and Levitt P (1993) Immunocytochemical demonstration of early appearing astroglial structures that form boundaries and pathways along axon tracts in the fetal brain. J Comp Neurol 328: 415–436Google Scholar
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    Snow DM, Lemmon V, Carrino DR, Caplan A and Silver JR (1990) Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp Neurol 109: 111–130Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Jerry Silver
    • 1
  1. 1.Department of Neurosciences, School of MedicineCase Western Reserve UniversityClevelandUSA

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