STEROID REGULATION OF DROSOPHILA PROGRAMMED CELL DEATH

果蝇程序性细胞死亡的类固醇调节

• 批准号: 6494610
• 负责人: Eric H Baehrecke
• 金额: $ 2.3万
• 依托单位: UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6494610
• 关键词: Drosophilidae; acridines; apoptosis; ecdysone; gene expression; genetic markers; genetic regulation; genetic transcription; hormone regulation /control mechanism; life cycle; metamorphosis; mutant; phenotype; salivary glands; scanning electron microscopy; stainings; steroid hormone

Steroid hormones regulate diverse metabolic, reproductive, and developmental processes throughout eukaryotes, and play an important role in human health. Relatively little is known about how steroids induce cell-specific biological responses, even though we know extensive details about how steroids activate gene transcription. We are utilizing the fruit fly, Drosophila melanogaster, as a system to study steroid-activated programmed cell death. Pulses of the steroid 20- hydoxyecdysone (ecdysone) trigger genetic regulatory hierarchies that mediate the destruction of the larval tissues by programmed cell death during metamorphosis of Drosophila from a larva to an adult. We have made progress toward understanding the mechanisms underlying steroid- regulated programmed cell death, by characterizing the relationship of genes that function in steroid-activated destruction of larval tissues. Our studies have emphasized the relationship between the ecdysone- regulated E93 gene, and the programmed cell death genes rpr and hid. E93 is unique compared to previously isolated ecdysone-regulated genes - E93 is specifically expressed in cells that are fated to die, while other early genes respond to each pulse of ecdysone in most cell types. In addition, E93 expression immediately precedes transcription of the programmed cell death genes rpr and hid. Most significantly, ectopic expression of E93 is sufficient to induce programmed cell death, and animals lacking E93 function have larval salivary glands that fail to die. Thus, E93 may be the primary stage- and tissue-specific mediator of steroid-regulated programmed cell death during Drosophila development. Here we propose: (1) detailed characterization of E93 mutants, (2) determination of the relationship between E93 and previously identified genes that function in cell death, and (3) isolation and characterization of targets of E93 that function in programmed cell death. These studies will lead to a better under- standing of this novel cell death pathway, and how steroids activate programmed cell death in higher eukaryotes.

类固醇激素调节多种代谢、生殖和 在整个真核生物的发育过程中发挥着重要作用 对人类健康的作用。 人们对类固醇如何发挥作用知之甚少 诱导细胞特异性的生物反应，尽管我们知道广泛 有关类固醇如何激活基因转录的详细信息。 我们是 利用果蝇（Drosophila melanogaster）作为研究系统 类固醇激活的程序性细胞死亡。 类固醇脉冲 20- 羟蜕皮酮（ecdysone）触发遗传调控层次结构 通过程序性细胞死亡介导幼虫组织的破坏 果蝇从幼虫到成虫的变态过程。 我们有 在理解类固醇背后的机制方面取得了进展 通过表征以下关系来调节程序性细胞死亡 在类固醇激活的幼虫组织破坏中起作用的基因。 我们的研究强调了蜕皮激素之间的关系 调节E93基因，以及程序性细胞死亡基因rpr和hid。 与之前分离的蜕皮激素调节基因相比，E93 是独特的 - E93在注定要死亡的细胞中特异性表达，而 在大多数细胞类型中，其他早期基因对每次蜕皮激素脉冲都有反应。 此外，E93 表达紧接在转录之前 程序性细胞死亡基因 rpr 和 hid。最重要的是，异位 E93的表达足以诱导程序性细胞死亡，并且 缺乏E93功能的动物的幼虫唾液腺无法 死。 因此，E93 可能是初级阶段和组织特异性介质 果蝇期间类固醇调节的程序性细胞死亡 发展。在这里我们建议：（1）E93的详细表征 突变体，(2)确定E93与 先前鉴定出在细胞死亡中起作用的基因，以及（3） E93 靶标的分离和表征 程序性细胞死亡。 这些研究将带来更好的基础 这种新的细胞死亡途径的现状，以及类固醇如何激活 高等真核生物中的程序性细胞死亡。