Alan R. Johnson

An analysis of astrocytic cell lines with different abilities to promote axon growth

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin and N-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.

REGENERATION IN THE VERTEBRATE CENTRAL NERVOUS SYSTEM: PHYLOGENY, ONTOGENY, AND MECHANISMS

(i) Cyclostomes . . . . . . (ii) Teleost fish . . . . . . (iii) Urodele amphibia . . . . . (iv) Anuran amphibia , . , (v) Reptiles . . . . . . . (vi) Birds . . . . . . . ( b ) Mammals . . . . . . . (i) Spinal cord . . . . . . (ii) Olfactory neurons . . . . . (iii) Retina . . . . . . . (iv) Hypothalamic-hypophysial system . . (v) Hippocampus . . . . . . (vi) Unmyelinated monoaminergic axons . 111. Ontogeny . . . . . . . . IV. Mechanisms . . . . . . . . (u) Intrinsic neuronal factors . . . . (b ) Environmental factors . . . . . ( i ) Oligodendrocytes and myelin . . . (ii) Astrocytes and glial scarring . . . (iii) Macrophages/microglia . . . . (iv) Axon growth-promoting molecules . . (v) Axon growth-inhibitory molecules . . (c) Axon response. . . . . . . V. Summary . , , . . , . , VI. Conclusions . . . . . . . . VII. Acknowledgements . . . . . . VIII. References . . . . . . . . ( a ) Non-mammalian vertebrates . , . . . . . . . 5 97

Contact inhibition of growth cone motility during neural development and regeneration

Abstract The potential importance of contact inhibition for neural development and regeneration has only recently been recognised. Growth cones have been shown to undergo abrupt collapse following contact with various cell types in vitro, including other neurons, and the collapse phenomenon is now being exploited to isolate and characterise the relevant molecules. Identifying the underlying mechanisms, which may involve ligand-receptor interactions, will be necessary for a full understanding of both axon guidance and the failure of axons to regenerate in the CNS of higher vertebrates.