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.

Expression of a transgene encoding only the laminin-like domain of UNC-6 is sufficient to guide cell and axon migrations and can disrupt fasciculation of ventral nerve cord axons

Yoo-Shick Lim, Smita Mallapur, William G. Wadsworth

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.