The genetics of social feeding behaviour in Caenorhabditis elegans

Natural isolates of Caenorhabditis elegans exhibit either social or solitary feeding behaviour. Animals from social strains aggregate and feed in groups on a bacterial lawn. In contrast, well-fed animals from solitary strains feed alone. This behavioural variation is associated with a single amino acid polymorphism in NPR-1, an RFamide receptor. Null mutations in npr-1 transform solitary wild strains into strongly social animals, indicating that npr-1 suppresses social feeding. To define molecules required for social feeding, I have mutagenised social npr-1(null) animals and selected mutants that feed alone. After screening 19200 haploid genomes, 150 mutants that show varying degrees of suppression of social feeding have been isolated. I have behaviourally characterised a subset of these mutants and mapped them to small chromosomal intervals. Amongst these are five X-linked mutations that fail to complement one another and map to a 50 kb interval. All five alleles strongly suppress aggregation behaviour, but show little or no other behavioural defects. Transgenic rescue experiments and sequencing data reveal that these alleles all disrupt gcy-36, one of the seven C. elegans homologues of human soluble guanylate cyclase (sGC). In mammals, sGCs are involved in neuronal signalling, axon guidance and maintenance of vascular tone, and are activated by nitric oxide. Since no nitric oxide synthase has been found in the C. elegans genome, these sGCs are likely regulated by a different, novel mechanism. Transgenic studies suggest that the cGMP-gated ion channel subunit tax-4 is required in one or more of the body cavity neurones AQR, PQR and URX for social feeding behaviour. These neurones directly contact the body fluid, and appear to integrate antagonistic signals to control social feeding. I have shown that gcy-365 is expressed in AQR, PQR and URX and that GFP-tagged GCY-36 protein is enriched in the membrane-dense cilia of AQR and PQR, suggesting that GCY-36 may be targeted to the membrane.EThOS - Electronic Theses Online ServiceGBUnited Kingdo