ECDYSONE RECEPTOR REQUIREMENTS IN DROSOPHILA DEVELOPMENT

从昆虫到人类，许多动物的各种发育过程都需要激素信号。 激素及其受体的缺陷与许多医学缺陷和疾病有关，包括癌症，发育和生殖障碍。 这些激素的受体作为配体激活的转录调节因子发挥作用（Evans，1988）。事实上，这些激素分子启动了如此多的专门和严格调控的机制，使得这些途径的研究和阐明成为一项极其复杂的奋进。 为了完成这项任务，果蝇动物系统因其经济有效的遗传操作手段而被招募。 类固醇激素蜕皮激素在果蝇发育期间起触发蜕皮和变态的作用。蜕皮激素脉冲发生在非常特定的时间间隔和在一定的浓度水平在果蝇发育。唯一已知的蜕皮激素受体分子，蜕皮激素受体蛋白（EcR），是一种核受体[沿着其异二聚体伴侣，超螺旋蛋白（USP）]结合蜕皮激素并促进靶基因的转录。 EcR蛋白至少有三种亚型（EcR-A、EcR-B1和EcR-B2），并且根据其独特的表达模式，假设每种亚型都具有不同的空间和/或时间活性（塔尔博特. 1993），以及它们独特的突变体表型分析（Bender，1997）。 这些数据表明，异构体在蜕皮激素诱导的正确信号传导途径的协调中发挥关键作用。 本项目的目标是从分子水平上确定果蝇发育过程中对EcR-A的需求。

Hormone signaling is required in a variety of developmental processes in a host of animals, from insects to humans. Defects in hormones and their receptors are associated with many medical defects and diseases, including cancers, developmental and reproductive disorders. The receptors of these hormones function as ligand activated transcriptional regulators (Evans, 1988). The fact that these hormone molecules initiate so many specialized and tightly regulated mechanisms, makes the investigation and elucidation of these pathways an extremely complicated endeavor. For this task the Drosophila animal system has been recruited for its economical and efficient means of genetic manipulation. The steroid hormone ecdysone acts to trigger molting and metamorphosis during Drosophila development. Ecdysone pulses occur at very specific intervals and at definite concentration levels during Drosophila development. The only known receptor molecule for ecdysone, ecdysone receptor protein (EcR), is a nuclear receptor that [along with its heterodimeric partner, ultraspiracle protein (USP)] binds ecdysone and promotes the transcription of target genes. There are at least three isoforms of the EcR protein, (EcR-A, EcR-B1, and EcR-B2) and each is hypothesized to have separate spatial and/or temporal activities, based on their unique expression patterns (Talbot. 1993), and their unique mutant phenotype analyses (Bender, 1997). This data suggests that the isoforms play a key role in the coordination of the correct signaling paths induced by ecdysone. The goals of this project are to molecularly determine the requirements of the EcR-A during Drosophila melanogaster development.