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Gitai Z, Tessier-Lavigne M, & Bargmann CI (1998). UNC-6 CAN REDIRECT AXONS IN VIVO presented in West Coast Worm Meeting. Unpublished information; cite only with author permission.
The UNC-6 netrin is thought to be involved in both the attraction and repulsion of circumferentially migrating cells and axons. Consistent with that idea, such migrations are disrupted in unc-6 mutants. It has also been shown that in vitro, the UNC-6 vertebrate homolog, Netrin-1, is sufficient to elicit both axonal outgrowth and turning. However, it has yet to be clearly demonstrated whether UNC-6 can play an instructive role in directing axon migrations in vivo. To address that question we have focused on the HSN motor neuron. In wild type animals UNC-6 is expressed ventrally, and the HSNUs initial axon projection is directed ventrally. The disruption of this ventral migration is one of the most penetrant defects associated with unc-6 mutants. We used the muscle-specific fragment of the UNC-129 promoter (kindly provided by Joe Culotti) to misexpress UNC-6 in the dorsal muscle. In an unc-6 mutant background, where the only source of UNC-6 is the ectopic dorsal source, the HSN axons can be misdirected dorsally. This shows that axons can be redirected to grow toward an ectopic source of UNC-6 in vivo. The attractive migration towards UNC-6 requires the UNC-40 receptor. Little is known, however, about the mechanism by which UNC-6Us interaction with UNC-40 signals to the cyctoskeleton to elicit directed migration. Axon growth cones are normally exposed to many different signals directing their growth. In worms with ectopic dorsal UNC-6, we appear to have migrations directed solely by UNC-6. This strain can now be used to identify and study molecules required for presentation, reception, and transduction of the UNC-6 / UNC-40 signal.
Affiliation:
- HHMI and Department of Biochemistry University of California, San Francisco San Francisco, CA 94143-0452, USA