Multiple netrin UNC-6 cues that act globally and locally are hypothesized to guide axons during formation of the C. elegans axon scaffold. We show that modifying local UNC-6 sources by ectopic expression and cell ablations will alter the patterning of surrounding nerves. Furthermore, we describe the in vivo responses of the SDQR axon. During the L1 stage this axon dorsally migrates away from ventral UNC-6 sources and then turns anteriorly along the dorsal sublateral nerve. In transgenic animals, we observe that the axon will migrate towards and along ectopic UNC-6 sources. In addition, this axon is guided ventrally in
unc-6(-) mutants, suggesting it also responds to another cue(s). Finally, if its dorsal target, the dorsal sublateral nerve, is absent, the SDQR axon will nevertheless turn and migrate anteriorly at the dorsal sublateral position, indicating that the nerve is not required for this decision. SDQR axon migrations are mediated by UNC-5 and UNC-40 cell surface proteins. In
unc-5(-) mutants the axon migrates ventrally, while in
unc-40(-) mutants the migration shows no dorsoventral preference. Ectopic
unc-6 expression has little influence on migrations in
unc-5(-) mutants, however in
unc-40(-) mutants it rescues the dorsal migration. We propose that UNC-6 acts synergistically with other cues to dorsoventrally position axons and that UNC-5 is necessary for the SDQR response to UNC-6 while UNC-40 enhances this response.