EGF receptor mediated signaling in Drosphilia

果蝇中 EGF 受体介导的信号传导

• 批准号: 7759218
• 负责人: Gertrud M. Schupbach
• 金额: $ 28.97万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7759218
• 关键词: Affect; Anterior; Aubergine; BRCA2 gene; Behavior; Biochemical; Biological Models; Candidate Disease Gene; Cell Communication; Cell Cycle; Cell Differentiation process; Cell Nucleus; Cells; Coupled; Couples; Cytoplasm; DNA; DNA Repair; Development; Dorsal; Drosophila Egfr protein; Drosophila genus; Drosophila melanogaster; Egg Shell; Embryo; Enhancers; Epidermal Growth Factor Receptor; Epithelial; Epithelial Cells; Epithelium; Event; Female; Gene Order; Gene Targeting; Genes; Genetic; Genetic screening method; Goals; Homologous Gene; Human; Ligands; Link; Malignant Neoplasms; Mediating; Meiosis; MicroRNAs; Modification; Molecular; Morphology; Mutation; Nature; Oocytes; Oogenesis; Ovarian Follicle; Ovary; Pathway interactions; Pattern; Phosphotransferases; Play; Process; Production; Proteins; RNA; RNA Interference; Receptor Activation; Receptor Protein-Tyrosine Kinases; Regulation; Repression; Research; Research Personnel; Research Project Grants; Role; Signal Transduction; Squash; System; Testing; Tissues; Transforming Growth Factor alpha; Translational Regulation; Translations; Work; computerized data processing; egg; insight; malignant breast neoplasm; mei-41; novel; programs; protein distribution; receptor; receptor-mediated signaling; repaired; research study; response; translation factor

DESCRIPTION (provided by applicant): Cell-cell communication plays an important role in the development of many tissues. We are studying signaling processes between the female germline and its surrounding follicle cells in the ovary of Drosophila melanogaster. We have shown that the Drosophila homolog of the Epidermal Growth Factor Receptor (Egfr) is expressed in the follicle cells and receives a highly controlled signal from the germline encoded by the gene gurken. Restricted activation of the Egfr by Gurken (a TGF-alpha like protein) initiates several different follicle cell responses and is required for axis formation of the egg and embryo. Our goal is to study the regulation of signal production in the germline and the patterning and differentiation processes that are activated in the follicle cells in response to receptor activation. Our specific aims are: 1) Analysis of a meiotic checkpoint mechanism that regulates Gurken translation. We have shown that DMA repair during meiosis is coupled via a meiotic checkpoint to translational control of Gurken in the oocyte cytoplasm. We will analyze genes that act in this pathway using both genetic and biochemical approaches. 2) Translational regulation of Gurken RNA. We will determine how the meiotic checkpoint regulates translation of Gurken as well as investigating other mechanisms of translational control that operate on Gurken. This will involve analysis of the gene Vasa as well as three new genes that we have found to affect Gurken protein levels. 3) Analysis of the response pathway acting in the follicle cells of the ovary. We have defined several specific patterning responses to Egfr activation in the follicle cells. In addition, the Egfr is also required for survival and normal cellular differentiation of the follicle cells. We will identify and analyze target genes acting downstream in these processes. This will involve the analysis of new mutations identified in mosaic follicle cell screens. Mutations in checkpoint genes, as well as unregulated activation of the human homologs of Egfr have been implicated in several forms of cancer, notably breast cancer. Our work will elucidate new roles of checkpoint genes, as well as analyzing the normal cellular pathways that regulate the activity of this receptor. It will also define downstream effector pathways operating in the follicle cell epithelium, which serves as a model system for epithelial development and differentiation.

描述（由申请人提供）：细胞间通讯在许多组织的发育中发挥着重要作用。我们正在研究果蝇卵巢中雌性种系与其周围卵泡细胞之间的信号传导过程。我们已经证明，表皮生长因子受体 (Egfr) 的果蝇同源物在毛囊细胞中表达，并接收来自 gurken 基因编码的种系的高度控制信号。 Gurken（一种 TGF-α 样蛋白）对 Egfr 的限制性激活会引发几种不同的卵泡细胞反应，并且是卵子和胚胎轴形成所必需的。我们的目标是研究种系信号产生的调节以及毛囊细胞响应受体激活而激活的模式形成和分化过程。我们的具体目标是：1）分析调节 Gurken 翻译的减数分裂检查点机制。我们已经证明，减数分裂过程中的 DMA 修复通过减数分裂检查点与卵母细胞细胞质中 Gurken 的翻译控制相结合。我们将使用遗传和生化方法分析在此途径中起作用的基因。 2) Gurken RNA 的翻译调控。我们将确定减数分裂检查点如何调节 Gurken 的翻译，并研究对 Gurken 起作用的其他翻译控制机制。这将涉及对 Vasa 基因以及我们发现影响 Gurken 蛋白质水平的三个新基因的分析。 3）作用于卵巢卵泡细胞的反应途径分析。我们已经定义了滤泡细胞中 Egfr 激活的几种特定模式反应。此外，Egfr 也是卵泡细胞生存和正常细胞分化所必需的。我们将识别并分析在这些过程下游发挥作用的靶基因。这将涉及对镶嵌卵泡细胞筛选中发现的新突变进行分析。检查点基因的突变以及人类 Egfr 同源物的不受调控的激活与多种癌症（尤其是乳腺癌）有关。我们的工作将阐明检查点基因的新作用，并分析调节该受体活性的正常细胞途径。它还将定义在滤泡细胞上皮中运行的下游效应通路，滤泡细胞上皮作为上皮发育和分化的模型系统。