UNC-119 and axon outgrowth: Toward a mechanism

Materi, W. and . Pilgrim D.

Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9, Canada.

UNC-119 is crucial for the correct development of the nematode nervous system. Worms mutant for the neuronally-expressed unc-119 gene show locomotory and sensory abnormalities that are explained by structural defects resulting from aberrant nervous system development.

Direct examination of nervous system structure using GFP reporters shows that unc-119 mutants have a variety of neurite outgrowth defects. The axons of chemosensory amphids exhibit highly penetrant ventral elongation defects within the nerve ring while the axons of anterior mechanosensory neurons have similar elongation defects in the dorsal direction. These defects suggest a disruption of normal synaptic patterns that is sufficient to explain both the inability of unc-119 mutants to form dauer larvae and their inability to respond to touch. The ventral nerve cord is moderately to severely defasciculated in 50% of mutant worms, supporting a general role for UNC-119 in axon guidance.

Defects in the anteroposterior position of dorsolateral turns suggests an aberrant response to choice points. However, there are no circumferential pathfinding defects in motor neurons, similar to those seen in unc-6 , unc-5 or unc-40 mutants. Indeed, although some cell bodies are misplaced in unc-119 mutants, their axons are often correctly targeted, implying that turning at choice points is somewhat independent of other pathfinding mechanisms.

Expression and rescue experiments with functional UNC-119::GFP constructs suggest that it acts cell autonomously. Although sub-cellular localization of the rat homologue, RRG4, has been demonstrated within photoreceptor ribbon synapses, antibody studies in the worm are still in progress. Yeast two-hybrid experiments suggest that UNC-119 is involved in a novel neurite development signaling pathway that mediates interaction between basement membrane collagen's and an uncharacterized zinc-finger protein. We have used PCR-based reverse genetics to isolate strains bearing deletions in the latter of these and have observed a lack of exploratory behavior but otherwise normal locomotion and response to touch stimuli.