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| Status |
Public on Oct 11, 2007 |
| Title |
Methylmercury treatment (rand-affy-droso-366220) |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by array
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| Summary |
Methylmercury (MeHg) toxicity in humans manifests deficits in neurological function. Cases of prenatal exposure to mercury have established that the developing nervous system is most highly susceptible to perturbation by MeHg. At a cellular level, MeHg-induced defects result from altered neuronal proliferation, migration and pathfinding. However, the molecular targets of MeHg that give rise to these outcomes are not fully understood. In an overall effort to identify the fundamental molecular targets of MeHg in neural development, we are investigating the effects of MeHg on gene expression and protein function in the Drosophila model. Since the fundamental signaling pathways in development of multicellular animals have been extensively characterized in Drosophila, and demonstrate high degree of conservation in vertebrates, we believe these data will lead us to the most pertinent pathways affected by MeHg and begin to elucidate the mechanism of MeHg neural toxicity relevant to cases of human exposure to this prevalent environmental toxin.
Our aim is to identify fundamental signaling pathways in neural development that are targets for MeHg poisoning.
Our hypothesis is that MeHg, by direct interaction with cysteine thiol groups, alters the function signaling pathway proteins and subsequently alters transcription of target genes in the respective pathways. Our hypothesis is supported by our recent data demonstrating a direct action of MeHg in activating the Notch receptor pathway and upregulating target gene expression. We anticipate a microarray analysis will elucidate additional fundamental signaling pathways where transcription is affected by this toxin.
Fertilized female flies are fed on food containing methylmercury (1-20 micromolar) or solvent control (DMSO) for a period of five days to allow for MeHg penetration in to eggs. Flies are then transfered to a cage for embryo collection for a discrete window of time (e.g. 1hr). Embryos are aged 16-24 hours and collected for total RNA extraction using the Trizol reagent. Total RNA is quantitated by spectrophotometry with a Nanodrop reader. While concentration dependent effects of MeHg are of interest, initial experiments will be conducted on samples exposed to a single concetration known to illicit effect in other bioassays (e.g. 10 micromolar). The goal is to see which genes are up- or down-regulated with MeHg exposure, as compared to control embryos that are not exposed. Emphasis in the analysis stage will be in identifying target genes of known signaling pathways.
Keywords: dose response
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| Contributor(s) |
Rand MD |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Oct 09, 2007 |
| Last update date |
Aug 28, 2018 |
| Contact name |
Winnie Liang |
| E-mail(s) |
[email protected]
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| Organization name |
Translational Genomics
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| Street address |
445 N. Fifth Street
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| City |
Phoenix |
| State/province |
AZ |
| ZIP/Postal code |
85012 |
| Country |
USA |
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| Platforms (1) |
| GPL1322 |
[Drosophila_2] Affymetrix Drosophila Genome 2.0 Array |
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| Samples (6)
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| GSM235403 |
Late Embryonic tissue, Whole brain: DMSO 1_le1 |
| GSM235404 |
Late Embryonic tissue, Whole brain: DMSO2_le1 |
| GSM235405 |
Late Embryonic tissue, Whole brain: DMSO3_le1 |
| GSM235406 |
whole animal, Whole brain: MeHg 1_le1 |
| GSM235407 |
whole animal, Whole brain: MeHg2_le1 |
| GSM235408 |
whole animal, Whole brain: MeHg3_le1 |
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| Relations |
| BioProject |
PRJNA102905 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9271_RAW.tar |
11.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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