We are studying aryl hydrocarbon receptor (AHR) signaling in Caenorhabditis elegans. The mammalian AHR is a ligand activated transcription factor, and it mediates the toxic effects of certain man-made pollutants. Endogenous ligands for AHR have not been identified, and the functions of AHR during normal development and homeostasis are not well understood. The C. elegans
ahr-1 and
aha-1 genes encode the orthologs of AHR and its dimerization partner ARNT, respectively. Our long-term goals are to elucidate the functions of
ahr-1 and
aha-1 and to use genetic strategies to identify potential endogenous regulators of
ahr-1 and
aha-1. Expression data suggest that
ahr-1 may have a role in neuronal development or function. AHR-1:GFP is expressed transiently in many neuronal cells coincident with differentiation. Additionally, AHR-1:GFP is expressed in a subset of chemosensory neurons in larvae and adults. To confirm and expand these studies, we are also attempting to generate AHR-1-specific antibodies. We constructed a library of EMS-mutagenized worms (approximately 6 x 105 haploid genomes) and used PCR to screen for deletion mutations in
ahr-1. We identified a 1.5 kb deletion that removes part of the PAS domain and introduces an early translational stop. C. elegans homozygous for
ahr-1 (
ia03) are viable, and they exhibit subtle locomotive abnormalities that are most evident when the animals move backwards.
ahr-1 does not appear to be required for dauer formation or for chemotaxis to several compounds tested. To investigate
ahr-1 requirements at a cellular level, we introduced the
unc-119:gfp neuronal marker into
ahr-1 (
ia03) mutants. Initially, we examined the cellular and axonal positions of AVM and SDQR, as they express AHR-1:GFP during the late L1 stage. In a majority of
ahr-1 (
ia03) mutants, SDQR is displaced ventrally and its axon projects laterally, rather than dorsally. We are currently characterizing this and other neuronal phenotypes in
ahr-1 (
ia03).