On the importance of being inhibited, or saying no to growth cones

Abstract

In considering what makes axons grow along certain pathways and not others, it is natural to look for cells and molecules to which neuronal growth cones adhere best or move over most rapidly. As with other forms of social intercourse, however, there are interactions between a growth cone and its cellular and matrix partners that are repulsive as well as seductive. In fact, several recent papers have described striking examples of growth cone retraction upon exposure to specific soluble molecules or upon contact with certain other axons. In addition, there is now evidence that the specificity of growth that retinal axons display on tectal cell membranes is due to an active inhibition of growth by the topographically inappropriate tectal membranes rather than an enhanced growth on the appropriate tectal membranes. Finally, the lack of axonal regeneration seen in the vertebrate CNS may be explained, in part, by two proteins on the surfaces of oligodendrocytes that inhibit neurite extension. Of possible clinical relevance is the recent finding that monoclonal antibodies against these inhibitory proteins can significantly enhance axonal regeneration in the optic nerve. These new result5 on the role of inhibition in process growth are briefly reviewed here.