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Drosophila melanogaster

ABSTRACT: Mechanisms of tumor-cells-invasion in Drosophila wing imaginal disc epithelia

PROVIDER: PRJDB12759 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	DRR334754_1.fastq.gz	Fastqsanger.gz
	DRR334754_2.fastq.gz	Fastqsanger.gz
	DRR334755_1.fastq.gz	Fastqsanger.gz
	DRR334755_2.fastq.gz	Fastqsanger.gz

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Identification of systemic injury response genes in Drosophila melanogaster

Project description:The systemic response to injury in Drosophila melanogaster is characterized by the activation of specific signaling pathways that facilitate the regeneration of wounded tissue and help coordinate wound healing with organism growth. The mechanisms by which damaged tissues influence the development and function of peripheral non-injured tissues is not fully understood. Injury was induced in early third instar larvae via temperature-dependent cell death in wing imaginal discs. Microarray analysis using RNA isolated from injured and control was used to identify genes underlying the systemic injury response. We identified 150 genes which were differentially expressed in response to localized cell death in wing imaginal discs. Upregulated genes were associated biological processes including carnitine biosynthesis, signal transduction and regulation of oxidoreductase activity while terms associated with downregulated genes included wound healing, imaginal disc-derived wing hair outgrowth, and regulation of glutamatergic synaptic transmission. Pathway analysis revealed that wing disc damage led to changes in fatty acid, cysteine, and carnitine metabolism. One gene, 14-3-3ζ, which encodes a known regulator of Ras/MAPK signaling was identified as a potential regulator of transdetermination during tissue regeneration. Our results raise the possibility that immune function and cell proliferation during wing disc repair and regeneration in Drosophila may require the sulfur amino acid cysteine and its’ metabolites, taurine and glutathione, similar to what has been reported during tissue repair in mammals. Further, it seems likely that imaginal disc damage stimulates the mobilization of fatty acids to support the energetically demanding process of tissue regeneration. The roles of additional genes that are differentially regulated following imaginal disc injury remain to be elucidated.

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Project description:In Drosophila, homozygosity for tumor suppressors, like lethal giant larvae, lgl, results in neoplastic transformation of imaginal disc epithelium - characterized by loss of their apico-basal polarity, unrestricted growth and invasion into neighboring tissues/organs. In genetic mosaics, however, lgl mutant clones are eliminated shortly after their initiation by cell competition. On the other hand, lgl mutant clones generated in Minute (M) genetic background, which compromises cell competition from the neighboring wild type cells, display clonal progression and tissue invasion. To gain insight into the molecular players of fly tumorigensis we undertook genome-wide transcriptional profiling of neoplastically transformed mosaic wing imaginal discs where lgl- clones were induced in M genetic background. Mosaic wing imaginal discs carrying wild type (lgl+) clones, also generated in M genetic background, served as controls. Transcriptional profile revealed up-regulation of a number of signaling pathways, such as Hippo, Wnt, TGF-beta or EGFR. Transcriptional profile of lgl- mosaic imaginal discs therefore provides a useful resource for identification of genes/pathways that are functionally relevant for carcinogenesis

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