Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification

Kuzin, B. A., Nikitina, E. A., Cherezov, R. O., Vorontsova, J. E., Slezinger, M. S., Zatsepina, O. G., Simonova, O. B., Enikolopov, G. N., Savvateeva-Popova, E. V. (April 2014) Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification. PLoS ONE, 9 (4). e94975. ISSN 1932-6203 (Electronic)1932-6203 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/24736732
DOI: 10.1371/journal.pone.0094975

Abstract

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.

Item Type: Paper
Subjects: organism description > animal > insect > Drosophila
organism description > animal behavior
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
organism description > animal behavior > memory
diseases & disorders > pulmonary disease > oxidative stress
CSHL Authors:
Communities: CSHL labs > Enikopolov lab
Depositing User: Matt Covey
Date: 20 April 2014
Date Deposited: 02 May 2014 14:22
Last Modified: 02 May 2014 14:22
PMCID: PMC3988104
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29956

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