Worms gang up on bacteria

BEHAVIOURAL GENETICS - The nematode worm Caenorhabditis elegans can be shy or gregarious when feeding time arrives. New work uncovers some of the neurons and genes that are involved in regulating social feeding in the worm, and points towards multiple systems of antagonistic signalling that control whether, and when, the worms aggregate into feeding groups. The standard laboratory strain of C. elegans is a loner, preferring solitary feeding. But worms with a valine-to-phenylalanine mutation at residue 215 of NPR-1 ”€ a putative G-protein-coupled receptor ”€ form aggregates when they encounter bacteria (their food source). Worms with a deletion at the npr-1 locus also aggregate, suggesting that a valine-containing receptor (NPR-1 215V) normally suppresses aggregation. In two studies, de Bono and colleagues take advantage of the excellent worm genetics and its small nervous system to delve deeper into the control of social feeding. The first study investigated how and where NPR-1 acts. The authors constructed a transgene that expressed GFP-tagged NPR-1 215V from the npr-1 promoter. When expressed in worms with an npr-1 deletion, this transgene suppressed aggregation. By using different promoters to drive transgene expression in subsets of neurons, the authors showed that expression in just three sensory neurons ”€ AQR, PQR and URX ”€ was sufficient to suppress aggregation. These three neurons are exposed to the fluid in the body cavity. Their ability to mediate social feeding seems to depend on signalling through a cyclic GMP-gated ion channel, as neuron-specific mutations in tax-2 or tax-4, which encode the subunits of the channel, also suppressed aggregation. So, it seems that NPR-1 suppresses aggregation by antagonizing signalling through TAX-2 and TAX-4 in these sensory neurons. The second study investigated how external stimuli might elicit aggregation. A screen for mutations that suppress aggregation in npr-1-deleted animals identified four genes. Two of these, osm-9 and ocr-2, are thought to encode subunits of a TRP-related cation channel in C. elegans chemosensory neurons, and are required for avoidance of various noxious stimuli. The other two genes, odr-4 and odr-8, are required to localize a subset of chemosensory receptors to sensory cilia. Analysis of GFP transgene expression in ocr-2; odr-4 double mutants showed that their expression is required in specific nociceptive neurons ”€ those that respond to noxious stimuli ”€ to rescue social feeding. Laser ablation of these neurons abolished social feeding, confirming the genetic data. Another piece of the puzzle came from studies of osm-3 mutants. OSM-3, a kinesin, is required for proper formation of sensory cilia on sensory neurons. Although removing osm-3 function interferes with the development of the crucial chemosensory neurons, it doesn't suppress social feeding. The authors propose that, as well as blocking the ability of these neurons to promote social feeding, lack of OSM-3 blocks antagonistic signals that normally inhibit this behaviour. Indeed, removing osm-3 function restores social feeding in odr-4 or ocr-2 mutants. So, as with the body cavity neurons, nociceptive neurons might be involved in a system of antagonism between signals that promote and suppress aggregation. As these neurons are required for responses to stressful or aversive stimuli, de Bono et al. propose that aggregation is a response to an aversive stimulus that is produced by bacteria. But what the aversive stimulus that promotes aggregation is and how the different control systems interact to regulate when social feeding occurs remains unknown. Rachel- Jones