STEROID REGULATION--DROSOPHILA PROGRAMMED CELL DEATH

类固醇激素调节多种代谢，生殖， 在整个真核生物的发育过程中， 在人类健康中的作用。 关于类固醇是如何 诱导细胞特异性生物反应，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 利用果蝇，果蝇，作为一个系统，研究 类固醇激活的程序性细胞死亡 类固醇的脉冲20- 羟蜕皮激素（蜕皮激素）触发遗传调节等级， 通过程序性细胞死亡介导幼虫组织的破坏 在果蝇从幼虫到成虫的蜕变过程中。 我们有 在了解类固醇的潜在机制方面取得了进展， 调节程序性细胞死亡，通过表征 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- 调控基因E93和程序性细胞死亡基因rpr和hid。 与以前分离的蜕皮激素调节基因相比，E93是独特的- E93在注定死亡的细胞中特异性表达，而 其他早期基因对大多数细胞类型中的蜕皮激素的每个脉冲作出反应。 此外，E93的表达紧接在E93的转录之前。 程序性细胞死亡基因RPR和HID。最重要的是， 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不能 死的 因此，E93可能是主要的阶段和组织特异性介质 类固醇调节的程序性细胞死亡 发展在此我们提出：（1）E93的详细表征 （2）确定E93与 先前鉴定的在细胞死亡中起作用的基因，和（3） 分离和表征E93靶，其在 程序性细胞死亡 这些研究将导致更好的下- 这种新的细胞死亡途径的立场，以及类固醇如何激活 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.