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

Autor: Kuzin BA; Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia; NBIC, Moscow Institute of Physics and Technology, Moscow, Russia., Nikitina EA; Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia., Cherezov RO; Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia., Vorontsova JE; Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia., Slezinger MS; Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia., Zatsepina OG; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia; NBIC, Moscow Institute of Physics and Technology, Moscow, Russia., Simonova OB; Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia., Enikolopov GN; NBIC, Moscow Institute of Physics and Technology, Moscow, Russia; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America., Savvateeva-Popova EV; Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2014 Apr 15; Vol. 9 (4), pp. e94975. Date of Electronic Publication: 2014 Apr 15 (Print Publication: 2014).
DOI: 10.1371/journal.pone.0094975
Abstrakt: 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.
Databáze: MEDLINE