The mammalian aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, and it mediates the toxic effects of dioxins and related compounds. Toxicological and genetic studies suggest that AHR regulates multiple developmental events, but the roles of AHR in neuronal development or function are not well understood. The C. elegans homologue of AHR is
ahr-1 (Powell-Coffman et al 1998, PNAS 95: 2844). To identify cells that express AHR-1, we constructed reporter genes in which the expression of GFP-tagged fusion proteins were directed by
ahr-1 regulatory sequences. During the first larval stage,
ahr-1:GFP is expressed in twenty-eight neurons, several blast cells, and two phasmid socket cells. The neurons that express
ahr-1:GFP represent multiple subtypes and include URXL, URXR, AQR and PQR, which directly contact pseudocoelomic fluid in the body cavity. Coates and de Bono (2002, Nature 419: 925) have demonstrated that these neurons modulate social feeding behavior. To further understand the role of the AHR-1 transcriptional complex in these and other neurons, we isolated and analyzed animals carrying a deletion in the
ahr-1 gene (Qin and Powell-Coffman 2004, Dev Biol. 270: 64). In collaboration with David Karow and Michael Marletta (U.C. Berkeley), we identified several genes that are expressed in URX, AQR, and PQR, including multiple soluble guanylate cyclases. We determined that expression of some cell-type-specific markers is dependent on
ahr-1 function, while expression of other markers appears to be
ahr-1-independent. Interestingly, a strong loss-of-function mutation in
ahr-1 partially suppresses social feeding behavior in
npr-1-deficient animals. These data suggest that
ahr-1 regulates a subset of the URX, AQR and PQR differentiation program. Further, specific
ahr-1-dependent genes may modulate social feeding behavior. We are currently using a combination of biochemical and genetic assays to examine these hypotheses and to further understand the role of
ahr-1 in neuronal development. C. elegans AHR-1 and mammalian AHR share many molecular and biochemical properties, but invertebrate AHR homologs do not bind dioxin. Experiments are in progress to assay the ability of murine AHR to rescue
ahr-1 function in URX neurons in the presence or absence of an activating ligand. This project is supported by NSF.