The wiring together of the nervous system during normal development, and the regeneration of damaged wiring in the mature nervous system, requires that neurons extend long axonal processes to their appropriate targets. There is considerable information available on some of the permissive guidance cues that encourage axon outgrowth. Less attention has been paid to outgrowth inhibiting cues. Recent evidence from several laboratories suggests that repulsive and inhibitory cues play a very important role in determining the trajectories of embryonic axons seeking their targets for the first time. There is also strong evidence that similar cues severely limit regeneration of mature connections that have been broken. We have discovered a glycoprotein in the embryonic nervous system of the chick that induces paralysis of the growing tips of extending axons. We propose to purify this factor, raise antibodies that recognize it, use the antibodies to study its distribution in vivo, and clone and sequence a cDNA corresponding to its message. We have also identified a biochemically distinct and more specifically targeted paralyzing activity from the adrenal medulla. We propose to develop enrichment steps for this activity, and to explore the relationship between it and a peripheral axonal label that induces the collapse of retinal growth cones.
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