Neuronal axons grow along highly specific routes to establish their normal connectivity during development. The growth cone at the tip of an extending axon uses inhomogeneously distributed guidance cues in its surrounding environment to decide where to extend. Some of these cues are attractive for specific growth cones while others are repulsive. Recent work suggests that there are a number of developmental systems in which repulsive cues play an important role in growth cone guidance. Repulsive guidance cues that persist in the mature central nervous system may also prevent the regeneration of damaged axons. We have recently purified, cloned, and sequenced collapsin, a likely repulsive guidance cue in the embryonic chick brain. Collapsin induces the paralysis of specific growth cones in an in vitro assay. Its mRNA is differentially expressed in the CNS and the periphery of developing embryos. It is partially homologous to a known axon guidance cue in insects. Here we propose to determine how collapsin could serve as a growth cone guidance cue by studying its distribution in vivo and its ability to steer growth cones when distributed in a gradient in vitro. We will test a growth cone repellent known to be secreted from the ventral nerve cord to determine if it is collapsin. Finally, the distribution and possible inhibitory properties of a molecule closely related to collapsin will be examined.
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