The long-term objective of this project is to understand the mechanisms by which neuronal projections are shaped. During development, growing axons respond to environmental cues at many points. One such cue, collapsin-1 (coll-1), has been shown to restrict the terminations of specific axon populations by a repulsive mechanism. In the olfactory bulb, coll-1 is initially expressed in a superficial band, during a period when olfactory axons pause at the bulb surface; subsequently, coll-1 expression shifts to deeper layers, and olfactory axons begin to penetrate into the bulb's outer layers. From these preliminary observations, we infer that coll-1 constrains the growth of olfactory endings: specifically, we predict that coll-1 acts early in development to exclude migrating olfactory axons from penetrating into the nascent olfactory bulb, and that later it contributes to the restriction of those axon terminations to a superficial layer. This proposal is designed to test that hypothesis by way of three Specific Aims: first, precisely defining the relationship between changing patterns of coll-1 expression in the developing bulb and the positions of migrating olfactory axons. Second, assessing the effect of ectopically-expressed coll-1 on the growth of these axons into chick olfactory bulb. Third, determining the pattern of olfactory axon trajectories in the absence of coll-1, in knock-out mice. Together these aims will help define the extent to which coll-1 directs the development of olfactory projections.
