Regulation of Caenorhabditis elegans avoidance behavior toward Pseudomonas aeruginosa PA14 by the canonical Wnt signaling pathway.

Using genetic and behavioral analyses, we identified a role for canonical Wnt/β-catenin signaling in the regulation of avoidance behavior toward Pseudomonas aeruginosa PA14 in Caenorhabditis elegans. RNAi analysis indicated a possible involvement of the Wnt ligand cwn-2, although interpretation of cwn-2 mutant phenotypes was limited by locomotor defects. Genetic and behavioral analyses further implicated the receptor cfz-2, the transducer dsh-1, and the β-catenin homologue bar-1 in this behavior, whereas gsk-3 acted as a negative regulator. Epistasis analyses further supported that cfz-2 functions genetically upstream of gsk-3 and bar-1 in the regulation of avoidance. Reporter analyses showed overlapping expression of cfz-2 and dsh-1 in a subset of head-region cells with neuron-like morphology, supporting a possible association between Wnt pathway expression and cells potentially relevant to avoidance-related regulation. However, these data do not establish a neuron-specific site of action. Systems-level analyses further indicated that genes identified through Wnt pathway screening are closely connected to known avoidance-related regulatory networks and are enriched in pathways associated with neuronal development, receptor-mediated signaling, and intercellular communication. Overall, these findings support a role for canonical Wnt/β-catenin signaling in PA14 avoidance and support a potential association between Wnt pathway activity and avoidance-related cellular or regulatory networks.