STEROID REGULATION OF DROSOPHILA PROGRAMMED CELL DEATH

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，起着重要的作用 对人类健康的作用。关于类固醇是如何 诱导细胞特异性的生物反应，即使我们知道广泛的 关于类固醇如何激活基因转录的详细信息。我们是 利用果蝇作为系统进行研究 类固醇激活的程序性细胞死亡。类固醇20的脉冲- 羟基蜕皮激素(蜕皮激素)触发遗传调节层次结构， 通过程序性细胞死亡调节幼虫组织的破坏 在果蝇从幼虫到成虫的变态过程中。我们有 在理解类固醇潜在的机制方面取得了进展- 调控的程序性细胞死亡，通过表征 在类固醇激活的破坏幼虫组织中起作用的基因。 我们的研究强调了蜕皮激素- 调控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控基因相比，E93是独一无二的- E93在注定要死亡的细胞中特异表达，而 在大多数细胞类型中，其他早期基因对蜕皮激素的每个脉冲都有反应。 此外，e93的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，异类 E93的表达足以诱导细胞程序性死亡，并且 缺乏e93功能的动物幼虫唾液腺不能 去死吧。因此，e93可能是主要的阶段和组织特异性的介体。 在果蝇中类固醇调节的程序性细胞死亡 发展。在此，我们提出：(1)e93的详细描述 突变体，(2)e93和E93之间关系的测定 之前发现的在细胞死亡中起作用的基因，以及(3) E93功能靶点的分离与鉴定 程序性细胞死亡。这些研究将导致更好的Under- 了解这一新的细胞死亡途径，以及类固醇是如何激活的 高等真核生物中的程序性细胞死亡。

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.