RUI: Tissue-Specific Gene Regulation in Drosophila

类固醇激素在高等生物体中控制着广泛的生理和发育过程，与受体蛋白共同作用，调节靶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的进步。值得注意的是，一种激素似乎能够引发截然不同的反应，这取决于细胞和时间背景。虽然关于类固醇受体如何控制培养的哺乳动物细胞转录的了解很多，但关于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阶段和组织特异性发育变化的了解很少。这个项目利用果蝇，黑腹果蝇，来研究类固醇诱导的基因表达变化如何控制发育过程中特定的细胞反应。类固醇20-羟基蜕皮酮(蜕皮激素)的脉冲触发遗传调控等级，通过程序性细胞死亡和形态发生(结构的形成)来指导组织的破坏。本项目的重点是核受体β-FTZ-F1和蜕皮激素受体在控制一组蜕皮激素诱导的早期基因的阶段和组织特异性表达中的作用，包括BR-C、E74A、E75A和E93。在对这些基因调控现象背后的分子机制的研究中，特别关注e93的调控。E93在死亡细胞中受到蜕皮激素的精确调控，在那里它诱导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提供了对激素做出反应的能力。该项目的目标是解决核受体超家族成员如何在发育过程中调节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起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.