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Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its  Drosophila  homolog  spineless  plays an important role in fly morphogenesis. We have previously shown that during morphogenesis  spineless  genetically interacts with  CG5017  gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of  spineless  and  CG5017  in pathways controlling oxidative stress response and long-term memory formation in  Drosophila melanogaster . Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of  spineless , mutation of  CG5017 , and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for  spineless ,  Cyp6g1  and  Gst-theta  genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of  spineless  and  CG5017  is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since  spineless  and  CG5017  are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

plos one

Combination of Hypomorphic Mutations of the Drosophila Homologues of Aryl Hydrocarbon Receptor and Nucleosome Assembly Protein Family Genes Disrupts Morphogenesis, Memory and Detoxification