Genome wide analysis of common and specific stress responses in adult drosophila melanogaster

BACKGROUND: During their life, multicellular organisms are challenged with oxidative stress. It is generated by several reactive oxygen species (ROS), may limit lifespan and has been related to several human diseases. ROS can generate a wide variety of defects in many cellular components and thus the response of the organism challenged with oxidative stress may share some features with other stress responses. Conversely, in spite of recent progress, a complete functional analysis of the transcriptional responses to different oxidative stresses in model organisms is still missing. In addition, the functional significance of observed transcriptional changes is still elusive. RESULTS: We used oligonucleotide microarrays to address the specificities of transcriptional responses of adult Drosophila to different stresses induced by paraquat and H(2)O(2), two oxidative stressors, and by tunicamycin which induces an endoplasmic reticulum (ER) stress. Both specific and common responses to the three stressors were observed and whole genome functional analysis identified several important classes of stress responsive genes. Within some functional classes, we observed that isozymes do not all behave similarly, which may reflect unsuspected functional specificities. Moreover, genetic experiments performed on a subset of lines bearing mutations in genes identified in microarray experiments showed that a significant number of these mutations may affect resistance of adult Drosophila to oxidative stress. CONCLUSIONS: A long term common stress response to paraquat- or H(2)O(2)-induced oxidative stresses and ER stress is observed for a significant number of genes. Besides this common response, the unexpected complexity of the stress responses to oxidative and ER stresses in Drosophila, suggest significant specificities in protective properties between genes associated to the same functional classes. According to our functional analysis, a large part of the genome may play a role in protective mechanisms against oxidative stress in Drosophila

Specific age related signatures in Drosophila body parts transcriptome

BACKGROUND: During the last two decades progress in the genetics of aging in invertebrate models such as C. elegans and D. melanogaster has clearly demonstrated the existence of regulatory pathways that control the rate of aging in these organisms, such as the insulin-like pathway, the Jun kinase pathway and the Sir2 deacetylase pathway. Moreover, it was rapidly shown that some of these pathways are conserved from yeast to humans. In parallel to genetic studies, genomic expression approches have given us significant information on the gene expression modifications that occur during aging either in wild type or long-lived mutant animals. But most of the genomic studies of invertebrate models have been performed so far on whole animals, while several recent studies in mammals have shown that the effects of aging are tissue specific. RESULTS: We used oligonucleotide microarrays to address the specificities of transcriptional responses in aging Drosophila in head, thorax or whole body. These fly parts are enriched in transcripts that represent different and complementary sets of genes. We present evidence for both specific and common transcriptional responses during the aging process in these tissues. About half of the genes described as downregulated with age are linked to reproduction and enriched in gonads. Greater downregulation of mitochondrial genes, activation of the JNK pathway and upregulation of proteasome subunits in the thorax of aged flies all suggest that muscle may be particularly sensitive to aging. Simultaneous age-related impairment of synaptic transmission gene expression is observed in fly heads. In addition, a detailed comparison with other microarray data indicates that in aged flies there are significant deviations from the canonical responses to oxidative stress and immune stress. CONCLUSION: Our data demonstrates the advantages and value of regionalized and comparative analysis of gene expression in aging animals. Adding to the age-regulated genes already identified in whole animal studies, it provides lists of new regionalized genes to be studied for their functional role in the aging process. This work also emphasizes the need for such experiments to reveal in greater detail the consequences of the transcriptional modifications induced by aging regulatory pathways

Pest Insect Olfaction in an Insecticide-Contaminated Environment: Info-Disruption or Hormesis Effect

Most animals, including pest insects, live in an “odor world” and depend strongly on chemical stimuli to get information on their biotic and abiotic environment. Although integrated pest management strategies including the use of insect growth regulators (IGRs) are increasingly developed, most insect pest treatments rely on neurotoxic chemicals. These molecules are known to disrupt synaptic transmission, affecting therefore sensory systems. The wide-spread use of neurotoxic insecticides and the growing use of IGRs result in residual accumulation of low concentrations in the environment. These insecticide residues could act as an “info-disruptor” by modifying the chemical communication system, and therefore decrease chances of reproduction in target insects. However, residues can also induce a non-expected hormesis effect by enhancing reproduction abilities. Low insecticide doses might thus induce adaptive processes in the olfactory pathway of target insects, favoring the development of resistance. The effect of sublethal doses of insecticides has mainly been studied in beneficial insects such as honeybees. We review here what is known on the effects of sublethal doses of insecticides on the olfactory system of insect pests

The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to septic injury in Drosophila

Septic injury triggers a rapid and widespread response in Drosophila adults that involves the up-regulation of many genes required to combat infection and for wound healing. Genome-wide expression profiling has already demonstrated that this response is controlled by signaling through the Toll, Imd, JAK-STAT and JNK pathways. Using oligonucleotide microarrays, we now demonstrate that the MAPKKK Mekk1 regulates a small subset of genes induced by septic injury including Turandot (Tot) stress genes. Our analysis indicates that Tot genes show a complex regulation pattern including signals from both the JAK-STAT and Imd pathways and Mekk1. Interestingly, Mekk1 flies are resistant to microbial infection but susceptible to paraquat, an inducer of oxidative stress. These results point to a role of Mekk1 in the protection against tissue damage and/or protein degradation and indicate complex interactions between stress and immune pathways in Drosophila

Identification et caractérisation de nouveaux gènes impliqués dans le viellissement et/ou la résistance aux stress oxydants chez l'organisme modèle Drosophila melanogaster

PARIS7-Bibliothèque centrale (751132105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Recherche et analyse de facteurs génétiques impliqués dans la résistance au stress et le contrôle de la longévité chez Drosophila melanogaster

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Chapitre 9: les autres modèles animaux alternatifs

International audienc

Endocytosis at the Drosophila blood–brain barrier as a function for sleep

International audienc

Effects of the different parameters of the model on lifespan.

<p><b>A, B.</b> As <b><i>a</i></b> increases, lifespan decreases and Smurf Increase Rate (SIR) increases. <b>C, D.</b> When <b><i>b</i></b> increases, lifespan increases without affecting the SIR but the first Smurfs appear later. <b>E, F.</b> An increase of <b><i>k</i></b> decreases both lifespan and the SIR. Thus, by measuring lifespan and SIR of flies in two distinct conditions indicates which parameter is affected by the treatment.</p

The remaining lifespan of individuals in phase 2 is similar in different drosophila strains.

<p><b>A.</b> Mated females from populations of 6 different genetic backgrounds show significant different lifespan curves, DGRP_83 (T₅₀ = 42 days; n = 128), DGRP_88 (T₅₀ = 39.6 days; n = 127), DGRP_91 (T₅₀ = 52.7 days; n = 340), DGRP_105 (T₅₀ = 57.1 days; n = 286), DGRP_136 (T₅₀ = 53.4 days; n = 243) and DGRP_195 (T₅₀ = 32.9 days; n = 262). <b>B, C.</b> The life expectancies of Smurfs from the 6 DGRP lines are highly similar, DGRP_83 (T₅₀ = 4.0 days; n = 31), DGRP_88 (T₅₀ = 2.3 days; n = 45), DGRP_91 (T₅₀ = 5.0 days; n = 96), DGRP_105 (T₅₀ = 3.1 days; n = 75), DGRP_136 (T₅₀ = 3.0 days; n = 56) and DGRP_195 (T₅₀ = 2.9 days; n = 63). In addition, none is different from the one measured using 1146 <i>drs</i>GFP individual flies (p > 0.05, 1-way ANOVA using the <i>drs</i>GFP as reference) although the Smurf survival measurement protocol was different. Error bars represent median ± s.e.m. <b>D-F.</b> Although SIRs of DGRP_195 (0.01832 ± 0.001602; R² = 0.5612) and DGRP_105 (0.003623 ± 0.001602; R² = 0.8127) are significantly different (p = 0.01579, N > 5 vials per genotype), it is possible to model the longevity curves of the two genotypes using the same <b><i>k</i></b> (phase 2) parameter (calculated from <i>drs</i>GFP Smurf flies–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141920#pone.0141920.g003" target="_blank">Fig 3C</a>) with R² > 0.99. Error bars represent mean ± s.e.m. <u><i>Note concerning Fig 4B and 4C</i>:</u><i>the T</i>_<i>50</i><i>are higher in fig C than B and this is due to averaging individual vials for the ANOVA test instead of calculating one T</i>_<i>50</i><i>using the whole population</i>.</p