IgCAMs Redundantly Control Axon Navigation in Caenorhabditis elegans

Background: Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) form one ofthe largest and most diverse families of adhesion molecules and receptors in the nervous system.Many members of this family mediate contact and communication among neurons duringdevelopment. The Caenorhabditis elegans genome contains a comparatively small number ofIgCAMs, most of which are evolutionarily conserved and found across all animal phyla. Only someof these have been functionally characterized so far.Results: We systematically analyzed previously uncharacterized IgCAMs in C. elegans. Greenfluorescent protein reporter constructs of 12 IgCAMs revealed that expression generally is notconfined to a single tissue and that all tissues express at least one of the IgCAMs. Most IgCAMswere expressed in neurons. Within the nervous system significant overlap in expression was foundin central components of the motor circuit, in particular the command interneurons, ventral cordmotoneurons as well as motoneurons innervating head muscles. Sensory neurons areunderrepresented among the cells expressing these IgCAMs. We isolated mutations for eight ofthe genes showing neuronal expression. Phenotypic analysis of single mutants revealed limitedneuronal defects, in particular axon navigation defects in some of the mutants. Systematic geneticinteraction studies uncovered two cases of functional overlap among three and four genes,respectively. A strain combining mutations in all eight genes is viable and shows no additionaldefects in the neurons that were analyzed, suggesting that genetic interactions among those genesare limited.Conclusion: Genetic interactions involving multiple IgCAMs affecting axon outgrowthdemonstrate functional overlap among IgCAMs during nervous system development.