Drosophila brain gene expression between wildtype and miR-34 null flies
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
SUBMITTER: Bonini Nancy
PROVIDER: E-GEOD-25008 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:gene expression profiles in fly brains between wildtype and miR-34 null flies
2011-12-23 | GSE25008 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24992: Drosophila brain microRNA expression with age: miRNA profiling GSE25007: Drosophila brain gene expression with age: mRNA profiling GSE25008: Drosophila brain gene expression between wildtype and miR-34 null flies Refer to individual Series. Aging is the most prominent risk factor for human neurodegenerative disease, but underlying mechanisms that connect two processes are less well characterized. With age, the brain undergoes functional decline and perhaps degeneration. Such decline may not just contribute to normal aging, but also enhance susceptibility to and progression of age-related neurodegenerative diseases. Therefore, defining intrinsic factors and pathways that underline the normal integrity of the adult nervous system may lead to insights that potentially link aging and neurodegeneration. Here, we report a highly conserved microRNA (miRNA), miR-34, as a modulator of aging and neurodegeneration. Using Drosophila, we show that fly miR-34 expression is brain-enriched and strikingly upregulated with age. Functional studies reveal that, whereas animals without miR-34 are normal as young adults, upon aging, they gradually show late-onset deficits characteristic of accelerated brain aging; these include a transcriptional signature of aged animals, coupled with rapid functional decline, loss of brain integrity, followed by a catastrophic decline in adult viability. Moreover, upregulation of miR-34 protects against neurodegeneration induced by pathogenic human polyglutamine (polyQ) disease protein. We next reveal a dramatic effect of miR-34 to silence the Eip74EF gene of steroid hormone pathways in the adult, which is crucial to maintain the normal aging. Collectively, these data define a miR-34-mediated mechanism that specifically affects long-term integrity of the adult nervous system. miR-34 function in Drosophila may thus present a link that functionally connects aging and neurodegeneration. Our studies implicate essential roles of miRNA- dependent pathways in maintenance of the adult brain, disease pathogenesis and healthy aging.
2011-12-23 | E-GEOD-25009 | biostudies-arrayexpress
Project description:We have shown previously that older flies are intrinsically more susceptible to Aβ42 toxicity. Building upon these findings, this study aimed to determine the mechanisms by which ageing increases this vulnerability to damage in the brain. A fixed dose of Aβ42 peptide was induced in young (5d) versus older (20d) fly neurons, and then gene and protein expression changes examined in dissected fly brains using microarray analyses. This unbiased approach has revealed genes and pathways that correlate with increased susceptibility of the ageing brain to proteotoxicity.
2021-04-07 | E-MTAB-8865 | biostudies-arrayexpress
Project description:microRNA expression profiles in fly brains with age microRNA expression profiles in fly brains, 3d, 30d and 60d
2011-12-23 | E-GEOD-24992 | biostudies-arrayexpress
Project description:Drosophila brain gene expression between wildtype and miR-34 null flies
| PRJNA142725 | ENA
Project description:Gene expression profile in fly brains during development
2011-12-23 | E-GEOD-25007 | biostudies-arrayexpress
Project description:Aging is a risk factor for neurodegenerative disease, but precise mechanisms that influence this relationship are still under investigation. Work in Drosophila melanogaster identified the microRNA miR-34 as a modifier of aging and neurodegeneration in the brain. MiR-34 mutants present aspects of early aging, including reduced lifespan, neurodegeneration, and a buildup of the repressive histone mark H3K27me3. To better understand how miR-34 regulated pathways contribute to age-associated phenotypes in the brain, here we transcriptionally profiled the miR-34 mutant brain. This identified that genes associated with translation are dysregulated in the miR-34 mutant. The brains of these animals show increased translation activity, accumulation of protein aggregation markers, and altered autophagy activity. To determine if altered H3K27me3 was responsible for this proteostasis dysregulation, we studied the effects of increased H3K27me3 by mutating the histone demethylase Utx. Reduced Utx activity enhanced neurodegeneration and mimicked the protein accumulation seen in miR-34 mutant brains. However, unlike the miR-34 mutant, Utx mutant brains did not show similar altered autophagy or translation activity, suggesting that additional miR-34-targeted pathways are involved. Transcriptional analysis of predicted miR-34 targets identified Lst8, a subunit of Tor Complex 1 (TORC1), as a potential target. We confirmed that miR-34 regulates the 3’ UTR of Lst8. Biological analysis of miR-34 mutant brains demonstrate that 4E-BP is hyperphosphorylated, consistent with increased Lst8 activity and changes in translation. Together, these results present novel understanding of brain aging and the role of the conserved miRNA miR-34 in impacting proteostasis in the brain with age.
2022-03-16 | GSE184559 | GEO
Project description:Flies were fed a normal diet or high-sugar (30% sucrose) diet for 7 days. Brains of flies fasted for 24h or sated were microdissected and immediately frozen in dry ice. The microdissection process from taking the fly out of the vial to freezing the brain took less than a minute. Each brain microdissected piece contains about 50K cells.We dissected 40 brains per condition (4 conditions total) and 4-5 biological replicates
2015-01-21 | ST000155 | MetabolomicsWorkbench
Project description:Spinocerebellar ataxia type 3 (SCA3) is one of the polyglutamine (polyQ) diseases, which are caused by a CAG repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain with mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insight into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified a set of genes that are differentially expressed specifically in CAG100 flies. Four independent replicates of flies expressing CAG0, CAG100, or CAA/G105 by elav-GAL4 were collected at 3 days. The transgenes are DsRed with either (CAG0) no CAG repeat in the 3'UTR, (CAG100) a CAG repeat of 100 CAGs in the 3'UTR, or (CAA/G105) an interrupted CAA CAG repeat in the 3'UTR (ref: Li et al., Nature 453:1107) The transgenes were adjusted to match in mRNA expression such that CAG0 flies had one copy of the transgene, CAG100 flies had 5 copies, and CAA/G105 had two copies. Fly brain tissue (about 20 brains per sample, dissected from head capsule, eyes, lamina and outer medulla removed) was dissected in cold phosphate buffered saline (PBS) and stored in Trizol reagent (Invitrogen Corporation, Carlsbad, CA) at -80Ë?C. Total brain RNA was extracted and purified using TRIzol reagent (Invitrogen) and the RNeasy Mini system (Qiagen), and treated with RNase-free DNase I (Qiagen). To define genes whose expression is altered in response to a toxic CAG repeat RNA, we compared CAG100 flies with age-matched flies expressing CAG0. To exclude transcriptional changes in response to a non-toxic trinucleotide repeat, a second gene list was generated by comparing CAA/G105 flies with age-matched CAG0 flies.
2011-11-22 | E-GEOD-31875 | biostudies-arrayexpress
Project description:Whole fly transcript profiles of changes upon induction of dFOXO in the gut and fat body using S1106>dFOXO flies and how this response changes when the feedback to foxo is removed in the foxo null background
2014-02-05 | E-MTAB-1232 | biostudies-arrayexpress