PDF(Pubmed)
Abstract：
Steroid hormones regulate tissue development and physiology by modulating the transcription of a broad spectrum of genes. In insects, the principal steroid hormones, ecdysteroids, trigger the expression of thousands of genes through a cascade of transcription factors (TFs) to coordinate developmental transitions such as larval molting and metamorphosis. However, whether ecdysteroid signaling can bypass transcriptional hierarchies to exert its function in individual developmental processes is unclear. Here, we report that a single non-TF effector gene mediates the transcriptional output of ecdysteroid signaling in Drosophila myoblast fusion, a critical step in muscle development and differentiation. Specifically, we show that the 20-hydroxyecdysone (commonly referred to as \"ecdysone\") secreted from an extraembryonic tissue, amnioserosa, acts on embryonic muscle cells to directly activate the expression of antisocial (ants), which encodes an essential scaffold protein enriched at the fusogenic synapse. Not only is ants transcription directly regulated by the heterodimeric ecdysone receptor complex composed of ecdysone receptor (EcR) and ultraspiracle (USP) via ecdysone-response elements but also more strikingly, expression of ants alone is sufficient to rescue the myoblast fusion defect in ecdysone signaling-deficient mutants. We further show that EcR/USP and a muscle-specific TF Twist synergistically activate ants expression in vitro and in vivo. Taken together, our study provides the first example of a steroid hormone directly activating the expression of a single key non-TF effector gene to regulate a developmental process via inter-organ signaling and provides a new paradigm for understanding steroid hormone signaling in other developmental and physiological processes.
摘要：
类固醇激素通过调节广谱基因的转录来调节组织发育和生理。在昆虫中，主要的类固醇激素，蜕皮类固醇,通过一系列转录因子（TFs）触发数千个基因的表达，以协调幼虫蜕皮和变态等发育转变。然而,蜕皮类固醇信号是否可以绕过转录层次以在个体发育过程中发挥其功能尚不清楚。这里,我们报道了单个非TF效应基因介导果蝇成肌细胞融合中蜕皮类固醇信号的转录输出，肌肉发育和分化的关键步骤。具体来说,我们显示20-羟基蜕皮激素（通常称为“蜕皮激素”）从胚外组织分泌，羊膜,作用于胚胎肌肉细胞直接激活反社会（蚂蚁）的表达，它编码在融合突触处富集的必需支架蛋白。不仅由蜕皮激素受体（EcR）和超吸虫（USP）组成的异二聚体蜕皮激素受体复合物通过蜕皮激素反应元件直接调节蚂蚁的转录，而且更引人注目的是，仅蚂蚁的表达就足以挽救蜕皮激素信号传导缺陷突变体中的成肌细胞融合缺陷。我们进一步显示EcR/USP和肌肉特异性TFTwist在体外和体内协同激活蚂蚁表达。一起来看,我们的研究提供了类固醇激素直接激活单个关键非TF效应基因的表达以通过器官间信号调节发育过程的第一个例子，并为理解其他发育和生理过程中的类固醇激素信号提供了新的范例。
