Genetic Control of Ecdysone Synthesis in Drosophila

在许多生物体中，生长主要发生在幼体的早期阶段。当达到特定的身体尺寸时，有机体停止生长，并过渡到性成熟成体(哺乳动物在青春期，昆虫在变态时)。然而，目前还不清楚当生物体足够大时，它们是如何感觉到这种转变的。果蝇的变态是由类固醇激素蜕皮激素触发的，蜕皮激素是在一种名为前胸腺(PG)的内分泌组织中合成的。蜕皮激素合成的一个关键激活剂是蛋白质激素PTTH。甲状旁腺激素的消除延迟了蜕皮激素的合成，并导致发育迟缓的大个子成虫的形成。PTTH触发蜕皮激素合成的PG内的细胞“机制”尚未确定，但这一确定对于了解变态的时间，从而最终的身体大小是如何调节的至关重要。本研究项目将验证甲状旁腺激素通过调节途径(MAP激酶途径)激活PG中的蜕皮激素合成的假说。抑制或激活MAP激酶途径的转基因将在PG中特异表达，以确定这些转基因是阻断PTTH诱导蜕皮激素合成的能力，还是在没有PTTH的情况下激活蜕皮激素合成。此外，转基因将用于增加或减少PTTH的合成，并将确定PTTH水平的变化对MAP激酶活性的影响。这些实验的成功完成将提供有关生物体用来控制发育过渡时间和最终身体大小的机制的基本信息。此外，该项目将通过培训遗传和分子技术方面的本科生和研究生研究人员来支持下一代科学家的发展。

In many organisms, growth occurs primarily during early juvenile phases. When a specific body size is reached, the organism stops growing and transitions to a sexually mature adult (at puberty in mammals and at metamorphosis in insects). Nevertheless, it is unclear how organisms sense when they are large enough for this transition. In the fruitfly, Drosophila, metamorphosis is triggered by the steroid hormone ecdysone, synthesized in an endocrine tissue called the prothoracic gland (PG). One key activator of ecdysone synthesis is the protein hormone, PTTH. Elimination of PTTH delays ecdysone synthesis and causes large and developmentally delayed adults to form. The cellular "machinery" within the PG by which PTTH triggers ecdysone synthesis has not been identified, and yet this identification is critical to understanding how the timing of metamorphosis, and hence final body size, is regulated. This research project will test the hypothesis that PTTH activates ecdysone synthesis via a regulatory pathway (MAP kinase pathway) in the PG. Transgenes inhibiting or activating the MAP kinase pathway will be expressed specifically in the PG to determine if these transgenes either block the ability of PTTH to induce ecdysone synthesis, or activate ecdysone synthesis in the absence of PTTH. In addition, transgenes will be used to increase or decrease PTTH synthesis, and the effects of changes in PTTH levels on MAP kinase activity will be determined. Successful completion of these experiments will provide essential information on the machinery used by organisms to control the timing of developmental transitions and hence final body size. In addition, this project will support the development of the next generation of scientists by training undergraduate and graduate researchers in genetic and molecular techniques.