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

项目总结 最近蚊媒疾病发病率急剧上升，如疟疾、寨卡病毒、基孔肯雅热和登革热 发热，以及蚊子对杀虫剂的广泛抗药性，强调了对昆虫采取新方法的必要性 以蚊子特效剂为基础的控制。这种针对蚊子的控制剂的发现取决于是否继续 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，是一种必需的 昆虫主要发育和生活史事件的调节者。昆虫和甲壳类起源于水生动物 四亿五千万年前入侵陆地生态系统的泛陆生动物祖先。耐甲氧丁二烯(Met) 蛋白质是昆虫JHS的胞内受体。Met对甲壳类动物Mf的反应能力表明 在六足动物与甲壳动物进化分离之前，Met在倍半萜信号中的作用 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生物合成和环氧化最后步骤的两种酶中的任何一种，甲基 转移酶(JHAMT)和P450环氧酶CYP15(EPOX)。缺乏Mf和JH的Jhamt-/-幼虫在发病时死亡 蜕变。而EPOX-/-突变体完成了整个生活史，它合成了Mf而没有JH。而EPOX-/- 成虫是有生育能力的，两性的繁殖性能都会急剧下降。使用这两个空突变体 对于蚊子，我们将研究在没有JH的情况下，MF如何足以完成成虫发育。我们的假设 IS 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，我们还将调查JH缺失型雌性的生殖适合度成本。我们希望能识别出这种分子 在我们的三个模型系(Jhamt-/-，EPOX-/-和WT)中JH信号差异的潜在机制。我们的两个零 突变的蚊子品系提供了一个独特的机会来探索未环氧化的与环氧化的JHS在 昆虫的发育和繁殖。完成拟议的研究可能导致确定以下目标 设计适合蚊子控制的新的、具体的和负担得起的战略。

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.