During nervous system development, axons navigate complex environments to reach synaptic targets. Early extending axons must interact with guidance cues in the surrounding tissue, while later extending axons can interact directly with earlier "pioneering" axons, "following" their path. In Caenorhabditis elegans, the AVG neuron pioneers the right axon tract of the ventral nerve cord. We previously found that
aex-3, a
rab-3 guanine nucleotide exchange factor, is essential for AVG axon navigation in a
nid-1 mutant background and that
aex-3 might be involved in trafficking of UNC-5, a receptor for the guidance cue UNC-6/netrin. Here we describe a new gene in this pathway:
ccd-5, a putative
cdk-5 binding partner.
ccd-5 mutants exhibit increased navigation defects of AVG pioneer as well as interneuron and motor neuron follower axons in a
nid-1 mutant background. We show that
ccd-5 acts in a pathway with
cdk-5,
aex-3 and
unc-5. Navigation defects of follower interneuron and motoneuron axons correlate with AVG pioneer axon defects. This suggests that
ccd-5 mostly affects pioneer axon navigation and that follower axon defects are largely a secondary consequence of pioneer navigation defects. To determine the consequences for nervous system function, we assessed various behavioural and movement parameters.
ccd-5 single mutants have no significant movement defects, and
nid-1 ccd-5 double mutants are less responsive to mechanosensory stimuli compared to
nid-1 single mutants. These surprisingly minor defects indicate either a high tolerance for axon guidance defects within the motor circuit and/or an ability to maintain synaptic connections among commonly misguided axons.