Worm Breeder's Gazette 15(3): 35 (June 1, 1998)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Department of Pathology, Robert Wood Johnson Medical School, Piscataway, NJ 08854
Netrin UNC-6 is a guidance cue for circumferential cell and axon migrations. It comprises two laminin-like domains( VI and V) and a C-domain that is unique to the netrin family. To study domain functions, we are expressing transgenes containing deletions or sequence swaps. The expression of a transgene encoding only the laminin-like domains( UNC-6DC) can rescue unc-6(-) null phenotypes including the defects in DTC migration, axon migration, and egg-laying. These rescuing activities require unc-40, and we are currently testing whether it also requires unc-5. Interestingly, the transgene causes a novel phenotype, both in the unc-6(-) and wild type backgrounds. A subset of ventral cord axons defasciculates and wanders across the ventral sublateral surface of the body wall. A ventral sublateral-lateral boundary is formed were the growth cones either collapse or turn longitudinally. The ventral muscle cells extend arms to this boundary where they form neuromuscular junctions with the mispositioned axons. Axons that normally migrate circumferentially are unaffected. The boundary phenotype is suppressed by unc-104(rh43), which encodes a kinesin required for neuronal vesicle transport and secretion of a muscle arm attractant(Hall and Hedgecock, Cell, Vol. 65, 837-847, 1991). The defasciculation phenotype is suppressed in unc-40(e1430) larvae. We conclude that the laminin-like domains of netrin UNC-6 are sufficient for the guidance activities. Further, we propose that there is an UNC-40-containing receptor complex on a subset of ventral axons and that UNC-6DC binding disrupts the complex and causes these axons to defasciculate. We are now characterizing which subset of ventral cord axons is affected.