wrk-1 and rig-5 control pioneer and follower axon navigation in the ventral nerve cord of Caenorhabditis elegans in a nid-1 mutant background.

During nervous system development, neurons send out axons, which must navigate large distances to reach synaptic targets. Axons grow out sequentially. The early outgrowing axons, pioneers, must integrate information from various guidance cues in their environment to determine the correct direction of outgrowth. Later outgrowing follower axons can at least in part navigate by adhering to pioneer axons. In Caenorhabditis elegans, the right side of the largest longitudinal axon tract, the ventral nerve cord, is pioneered by the AVG axon. How the AVG axon navigates is only partially understood. In this study, we describe the role of two members of the IgCAM family, wrk-1 and rig-5, in AVG axon navigation. While wrk-1 and rig-5 single mutants do not show AVG navigation defects, both mutants have highly penetrant pioneer and follower navigation defects in a nid-1 mutant background. Both mutations increase the fraction of follower axons following the misguided pioneer axon. We found that wrk-1 and rig-5 act in different genetic pathways, suggesting that we identified two pioneer-independent guidance pathways used by follower axons. We assessed general locomotion, mechanosensory responsiveness, and habituation to determine whether axonal navigation defects impact nervous system function. In rig-5 nid-1 double mutants, we found no significant defects in free movement behavior; however, a subpopulation of animals shows minor changes in response duration habituation after mechanosensory stimulation. These results suggest that guidance defects of axons in the motor circuit do not necessarily lead to major movement or behavioral defects but impact more complex behavioral modulation.