RUI: Tissue-Specific Gene Regulation in Drosophila

类固醇激素在高等生物中控制着广泛的生理和发育过程，与受体蛋白一起调节目标基因的阶段和组织特异性转录。类固醇受体遗传学和生物化学的研究使我们对类固醇如何激活基因转录的理解取得了巨大进展。值得注意的是，一种激素似乎能够根据细胞和时间背景诱导截然不同的反应。尽管对类固醇受体如何控制培养的哺乳动物细胞中的转录了解很多，但对这些对基因表达的影响如何导致与类固醇激素作用相关的戏剧性的阶段和组织特异性发育变化知之甚少。该项目利用果蝇（Drosophila melanogaster）来研究激素诱导的基因表达变化如何控制发育过程中的特定细胞反应。类固醇20-羟基蜕皮激素（蜕皮激素）的脉冲触发遗传调控等级，通过程序性细胞死亡指导组织的破坏和形态发生（结构的形成）。本项目主要研究核受体β - fz - f1和表皮蜕变激素受体在控制BR-C、E74A、E75A和E93等表皮蜕变激素诱导的“早期”基因的分期和组织特异性表达中的作用。在研究这些基因调控现象的分子机制时，我们特别关注E93的调控。E93在垂死细胞中受到蜕皮激素的精确调控，诱发程序性细胞死亡反应。在某些组织中，如幼虫唾液腺，蜕皮激素对E93的调节依赖于β - ftz - f1，它似乎为E93提供了对激素作出反应的能力。该项目的目标是研究核受体超家族成员在发育过程中如何调节E93以及BR-C、E74A和E75A的阶段和组织特异性表达，并阐明类固醇激素引发不同生物反应的机制。

Steroid hormones control a wide range of physiological and developmental processes in higher organisms, acting in conjunction with receptor proteins to regulate the stage- and tissue-specific transcription of target genes. The study of steroid receptor genetics and biochemistry has led to enormous advances in our understanding of how steroids activate gene transcription. Remarkably, a single hormone appears to be capable of inducing extremely different responses, depending on cellular and temporal context. Although much is understood about how steroid receptors control transcription in cultured mammalian cells, little is understood about how these effects on gene expression result in the dramatic stage- and tissue-specific developmental changes associated with steroid hormone action. This project makes use of the fruit fly, Drosophila melanogaster, to examine how steroid-induced changes in gene expression control specific cellular responses during development. Pulses of the steroid 20-hydroxyecdysone (ecdysone) trigger genetic regulatory hierarchies that direct both destruction of tissues by programmed cell death, and morphogenesis (the formation of structures). This project focuses on the roles of nuclear receptor beta-FTZ-F1 and the ecdysone receptor in controlling the stage- and tissue-specific expression of a set of ecdysone-inducible "early" genes, including BR-C, E74A, E75A and E93. In this examination of the molecular mechanism underlying these gene regulatory phenomena, particular attention is paid to the regulation of E93. E93 is precisely regulated by ecdysone in dying cells, where it induces a programmed cell death response. In certain tissues, such as the larval salivary gland, the regulation of E93 by ecdysone depends on beta-FTZ-F1, which appears to provide E93 with the competence to respond to the hormone. Goals of this project are to address how members of the nuclear receptor superfamily regulate the stage- and tissue-specific expression of E93, as well as BR-C, E74A, and E75A during development, and to shed light on the mechanisms by which steroid hormones elicit distinct biological responses.