FlyAtlas: database of gene expression in the tissues of Drosophila melanogaster

Robinson, Scott; Herzyk, Paweł; Dow, Julian A. T.; Leader, David P.

doi:10.1093/nar/gks1141

Cited by 163 publications

(183 citation statements)

References 7 publications

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“…The online atlas of gene expression, FlyAtlas.org, shows that both Nha1 and Nha2 are widely expressed, but particularly in the epithelia of the alimentary canal (15,23,24). To validate this pattern of gene expression, we performed quantitative real-time PCR, which demonstrated consistent enrichment levels at least as high as those seen in the Affymetrix-derived FlyAtlas (Fig.…”

Section: Resultsmentioning

confidence: 85%

Transport proteins NHA1 and NHA2 are essential for survival, but have distinct transport modalities

Chintapalli

Kato

Henderson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The cation/proton antiporter (CPA) family includes the well-known sodium/proton exchanger (NHE; SLC9A) family of Na + /H + exchangers, and the more recently discovered and less well understood CPA2s (SLC9B), found widely in living organisms. In Drosophila, as in humans, they are represented by two genes, Nha1 (Slc9b1) and Nha2 (Slc9b2), which are enriched and functionally significant in renal tubules. The importance of their role in organismal survival has not been investigated in animals, however. Here we show that single RNAi knockdowns of either Nha1 or Nha2 reduce survival and in combination are lethal. Knockdown of either gene alone results in up-regulation of the other, suggesting functional complementation of the two genes. Under salt stress, knockdown of either gene decreases survival, demonstrating a key role for the CPA2 family in ion homeostasis. This is specific to Na + stress; survival on K + intoxication is not affected by sodium/hydrogen antiporter (NHA) knockdown. A direct functional assay in Xenopus oocytes shows that Nha2 acts as a Na + /H + exchanger. In contrast, Nha1 expressed in Xenopus oocytes shows strong Cl − conductance and acts as a H + -Cl − cotransporter. The activity of Nha1 is inhibited by chloride-binding competitors 4,4′-diiso-thiocyano-2,2′-disulfonic acid stilbene and 4,4′-dibenzamido-2,2′-stilbenedisulphonate. Salt stress induces a massive up-regulation of NHA gene expression not in the major osmoregulatory tissues of the alimentary canal, but in the crop, cuticle, and associated tissues. Thus, it is necessary to revise the classical view of the coordination of different tissues in the coordination of the response to osmoregulatory stress.The NHA Gene Family Ionic homeostasis is essential for life and requires a significant fraction of an organism's total energy budget. Primary ion-motive ATPases provide electrochemical ion gradients to drive an array of channels, cotransporters, and antiporters. The cation/proton antiporter (CPA) family is ubiquitous and best known for the NHE, or CPA1, branch exemplified by the classical Na + /H + exchanger NHE1 (1, 2), which is a target for the potassium-sparing diuretic amiloride in the treatment of hypertension and congestive heart failure. More recently discovered are the sodium/hydrogen antiporters (NHAs), a subbranch of the CPA2 family, which is much less well understood (3, 4). Originally studied in bacteria, yeast, and plants (5, 6), this subbranch in humans includes two NHA genes in tandem: NHA1 (SLC9B1), which is testis-specific, and NHA2 (SLC9B2), which is ubiquitous (7,8).In osteoclasts, NHA2 colocalizes with the V-ATPase a3 subunit and the lysosomal marker LAMP2 (9), and resides in the plasma membrane of Madin-Darby canine kidney (MDCK) cells (7). In the pancreas, NHA2 is necessary for insulin secretion but localizes not to insulin-containing vesicles, but rather to transferrin-positive endocytic vesicles (4, 10). NHA2 also has been linked to hypertension (8). Thus, NHAs are multifunctional proteins expressed in a wide range of ...

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Section: Resultsmentioning

confidence: 85%

Transport proteins NHA1 and NHA2 are essential for survival, but have distinct transport modalities

Chintapalli

Kato

Henderson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Specifically, nutrient absorption occurs primarily in the insect midgut (Ohlstein and Spradling 2006;Buchon et al 2013), which might be expected to respond most rapidly to oral toxin intake. To address the issue we used two metrics, TP(i) and TSr(i), both of which combine our expression data sets with data available in the FlyAtlas database (Chintapalli et al 2007;Robinson et al 2013), a unique resource with tissue expression data collected across several dissected tissues. We observed that neither treatment with high sugar nor that with DEHP showed an overtly tissue-specific disruption in either sets of upregulated ( Figure S5) or downregulated ( Figure 2A) genes.…”

Section: Resultsmentioning

confidence: 99%

“…Tissue specificity of differentially expressed (DE) genes was assessed using the FlyAtlas (Chintapalli et al 2007;Robinson et al 2013). We filtered the data to include only a nonredundant set of adult tissues: brain, eye, adult thoracicoabdominal ganglion (tag), adult salivary gland (sg), testis, accessory glands (acc), crop, midgut, tubule, hindgut, heart, and adult fat body.…”

Section: Metrics Of Tissue Perturbationmentioning

confidence: 99%

High Intake of Dietary Sugar Enhances Bisphenol A (BPA) Disruption and Reveals Ribosome-Mediated Pathways of Toxicity

Branco¹,

Lemos²

2014

Genetics

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Bisphenol A (BPA) is an organic compound to which human populations are ubiquitously exposed. Epidemiological data suggest BPA exposure might be associated with higher rates of diabetes and reproductive anomalies. Health concerns also include transgenerational consequences, but these mechanisms are crudely defined. Similarly, little is known about synergistic interactions between BPA and other substances. Here we show that acute and chronic exposure to BPA causes genome-wide modulation of several functionally coherent genetic pathways in the fruit fly Drosophila melanogaster. In particular, BPA exposure causes massive downregulation of testis-specific genes and upregulation of ribosome-associated genes widely expressed across tissues. In addition, it causes the modulation of transposable elements that are specific to the ribosomal DNA loci, suggesting that nucleolar stress might contribute to BPA toxicity. The upregulation of ribosome-associated genes and the impairment of testis-specific gene expression are significantly enhanced upon BPA exposure with a high-sugar diet. Our results suggest that BPA and dietary sugar might functionally interact, with consequences to regulatory programs in both reproductive and somatic tissues. E XPOSURE to environmental toxins is widespread. It is well documented, for instance, that human populations are commonly exposed to bisphenol A (BPA), bis(2-ethylhexyl) phthalate (DEHP), dioxins, and other organic molecules produced at industrial scales. Toxins might act by modulating epigenetic pathways to change the expression of genes and normal cellular homeostasis and could result in transgenerational consequences. The fast pace at which new compounds are invented and become ubiquitous in the environment poses a challenge to safety assessment. This challenge emerges not only from the large number of compounds to evaluate, but also from the high dimensionality of toxic responses across tissue types and developmental stages. This is further aggravated by the potential for unexpected synergism among toxins in mixtures. Sensitivity might also be strongly dependent on the specific epigenomic features and genetic makeup of an individual (Du et al. 2004).Genomic analyses have uncovered levels of human genetic variation not surmised a few decades ago (e.g., Sudmant et al. 2010). Cost-effective epigenetic and physiological models are needed for (i) addressing tissue-specific responses to toxins, (ii) gaining insights into mechanisms of epigenetic toxicity, and (iii) evaluating the manifestation of these responses across naturally occurring genotypes. In particular, cost-effective models with massive publicly available genetic information (Zwarts et al. 2011; King et al. 2012a,b;Mackay et al. 2012) might allow for genome-wide evaluation of toxic responses and assessment of coexposure outcomes in conjunction with the evaluation of unique individual responses.BPA is one of the most abundantly produced chemicals worldwide, reaching an annual volume .4 million tons (Burridge 2003). Multi...

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“…A total of 1,931,250 SNPs and indels were used in our analyses, with the minor alleles present in at least seven DGRP lines, using only biallelic sites. For each tissue, we used FlyAtlas AffyCalls (23) to determine which genes were expressed in which tissue. To determine significance, we used a Fisher's exact test comparing the expected number of gene expressed in each tissue across the entire genome to the observed number of genes expressed in each tissue in our gene list.…”

Section: Methodsmentioning

confidence: 99%

Behavioral idiosyncrasy reveals genetic control of phenotypic variability

Ayroles

Buchanan²,

O’Leary

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

178

207

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Quantitative genetics has primarily focused on describing genetic effects on trait means and largely ignored the effect of alternative alleles on trait variability, potentially missing an important axis of genetic variation contributing to phenotypic differences among individuals. To study the genetic effects on individual-to-individual phenotypic variability (or intragenotypic variability), we used Drosophila inbred lines and measured the spontaneous locomotor behavior of flies walking individually in Y-shaped mazes, focusing on variability in locomotor handedness, an assay optimized to measure variability. We discovered that some lines had consistently high levels of intragenotypic variability among individuals, whereas lines with low variability behaved as although they tossed a coin at each left/right turn decision. We demonstrate that the degree of variability is itself heritable. Using a genome-wide association study (GWAS) for the degree of intragenotypic variability as the phenotype across lines, we identified several genes expressed in the brain that affect variability in handedness without affecting the mean. One of these genes, Ten-a, implicates a neuropil in the central complex of the fly brain as influencing the magnitude of behavioral variability, a brain region involved in sensory integration and locomotor coordination. We validated these results using genetic deficiencies, null alleles, and inducible RNAi transgenes. Our study reveals the constellation of phenotypes that can arise from a single genotype and shows that different genetic backgrounds differ dramatically in their propensity for phenotypic variabililty. Because traditional mean-focused GWASs ignore the contribution of variability to overall phenotypic variation, current methods may miss important links between genotype and phenotype.variability | variance QTL | DGRP | ten-a | personality

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FlyAtlas: database of gene expression in the tissues of Drosophila melanogaster

Cited by 163 publications

References 7 publications

Transport proteins NHA1 and NHA2 are essential for survival, but have distinct transport modalities

Transport proteins NHA1 and NHA2 are essential for survival, but have distinct transport modalities

High Intake of Dietary Sugar Enhances Bisphenol A (BPA) Disruption and Reveals Ribosome-Mediated Pathways of Toxicity

Behavioral idiosyncrasy reveals genetic control of phenotypic variability

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