How can mosquitoes develop and reproduce in the complete absence of juvenile hormone?

项目摘要 最近蚊子传播疾病的发病率急剧增加，如疟疾，寨卡病毒，基孔肯雅病毒和登革热 发烧和蚊子对杀虫剂的广泛抗药性强调了对昆虫新方法的需要。 基于蚊子特异性药剂的控制。这种蚊子特异性控制剂的发现取决于持续的 蚊子生物学的基础研究。保幼激素（JH）是一种环氧化的倍半萜类化合物， 昆虫主要发育和生活史事件的调节因子。昆虫和甲壳类动物起源于水生 4.5亿年前入侵陆地生态系统的泛甲壳类祖先。耐甲氧普仑（Met） 蛋白是昆虫JH的细胞内受体。Met对MF（甲壳类JH）的反应能力表明， Met在倍半萜类信号传导中的作用先于六足动物从甲壳类动物进化分离 血统为了解决MF环氧化的进化和生物学意义，我们完全产生了蚊子， 缺少催化MF/JH生物合成和环氧化的最后步骤的两种酶中的任一种， 转移酶（JHAMT）和P450环氧酶CYP 15（EPOX）。缺乏MF和JH的jhamt-/-幼虫在发病时死亡， 变态而合成MF而不合成JH的epox-/-突变体完成了整个生活史。而环氧树脂-/- 成年人是有生育能力的，两性的生殖能力都大大降低。利用这两个零突变株系 蚊子，我们将研究如何在没有JH，MF是足以完成成人的发展。我们的假设 MF能够适当地激活控制蚊子幼虫发育和变态的基因网络。 此外，我们将调查生殖健康成本在JH零女性。我们希望能识别出 在我们的三个模型系（jhamt-/-、epox-/-和WT）中JH信号传导差异的潜在机制。我们的两个空 突变的蚊子品系提供了一个独特的机会，探索非环氧化与环氧化JH的作用， 昆虫的发育和繁殖。完成拟议的研究可能会导致确定目标， 制定新的、具体的和负担得起的适合于控制蚊子的战略。

PROJECT SUMMARY Recent dramatic increases in the incidence of mosquito-borne diseases, like Malaria, Zika, Chikungunya and Dengue Fever, and the wide-spread resistance of mosquitoes to insecticides emphasizes the need for new approaches for insect control based on mosquito-specific agents. The discovery of such mosquito-specific control agents depends on continued basic research on the biology of mosquitoes. Juvenile hormone (JH), an epoxidated sesquiterpenoid, is an essential regulator of major developmental and life history events in insects. Insects and crustaceans originated from aquatic pancrustacean ancestors that invaded terrestrial ecosystems over 450 million years ago. The Methoprene-tolerant (Met) protein is the intracellular receptor for insect JHs. The ability of Met to respond to MF, the “crustacean JH”, suggests that the role of Met in sesquiterpenoid signaling precedes the evolutionary separation of the hexapoda from the crustacean lineages. To address the evolutionary and biological significance of MF epoxidation, we generated mosquitoes completely lacking either of the two enzymes that catalyze the last steps of MF/JH biosynthesis and epoxidation, the methyl transferase (JHAMT) and the P450 epoxidase CYP15 (EPOX). jhamt-/- larvae lacking both MF and JH died at the onset of metamorphosis. While epox-/- mutants, which synthesized MF but no JH completed the entire life cycle. While epox-/- adults are fertile, the reproductive performance of both sexes is dramatically reduced. Using these two lines of null mutant mosquitoes, we will investigate how in the absence of JH, MF is sufficient to complete adult development. Our hypothesis is MF is able to properly activate the gene networks that control mosquito larval development and metamorphosis. Additionally, we will investigate the reproductive fitness cost in JH null females. We expect to recognize the molecular mechanism underlying the differences in JH signaling in our three model lines (jhamt-/-, epox-/- and WT). Our two null mutant mosquito lines provide a unique opportunity to explore the role of non-epoxidated versus epoxidated JHs in the development and reproduction of insects. Completing the proposed research could lead to the identification of targets for designing new, specific and affordable strategies suitable for mosquito control.