The C. elegans intestine acts as a neurosecretory organ, releasing small molecules that affect multiple aspects of physiology, including dauer formation, locomotion and defecation. Dauer formation is cued by intestinal release of IGF-1 in low food situations. When animals are feeding, the intestine undergoes periodic calcium waves that control the motor steps of the defecation cycle; these waves invoke secretion of signaling molecules that regulate defecation. This calcium spike appears to trigger the release of at least one peptide, NLP-40. Recent findings from the Biron lab suggest that an intestinally-derived signal induces a brief locomotory reversal in synch with the calcium wave. We believe that the intestinal calcium wave induces the release of factors affecting social feeding behavior, the tendency for worms to feed in large clumps rather than individually.
Altering intestinal cell-cell communication via mutation of a gap junctional subunit, INX-16, leads to an increase in social feeding. Worms with mutated inx-16, have slow, backward, or failed intestinal calcium waves known to affect defecation steps and the defecation associated locomotory reversals. inx-16 mutants show a modest increase in social feeding (about 10% higher than N2). To determine whether the social feeding phenotype correlated broadly with defecation defects, we analyzed more defecation mutants: pbo-4, pbo-5 and aex-2. None of these exhibited a significant social feeding phenotype suggesting that the social feeding in inx-16 does not result from abnormal defecation in general.
To determine how inx-16 mutation interacted with the known social feeding pathways we combined inx-16 mutation with npr-1 or daf-7. Addition of an inx-16 mutation to a daf-7 mutant significantly increased social feeding levels, which suggests that these two pathways are at least partly independent. The npr-1;inx-16 double mutant produced a social feeding score similar to that of npr-1 alone. This suggests that NPR-1 acts in the same pathway as INX-16 to mediate social feeding. NPR-1 can be activated by the neuropeptide FLP-21, which is reportedly expressed in the intestine. We hypothesize that, in inx-16 mutants, abnormal intestinal calcium waves lead to defective FLP-21 secretion from the intestine and insufficient activation of NPR-1. Deletion of flp-21 results in enhanced social feeding similar to that of inx-16 mutation. Double mutants of inx-16 and flp-21 do not result in an additive increase in social feeding compared to single mutants. The intestinal calcium wave, itself dependent on feeding, appears to regulate the release FLP-21, thus modulating feeding behavior.