Specification of anterioposterior polarity in the mosquito, Chironomus

描述(申请人提供)：早期胚胎的遗传电路为种群替换策略提供了目标，这些策略在控制蚊子等疾病媒介方面具有重要的潜在应用。然而，蚊子的发育仍然知之甚少，因为目前这一组的研究集中在人类疾病媒介上，坚韧且大量着色的蛋壳阻碍了功能发育研究。本研究的目的是阐明决定库蚊胚胎前后(AP)极性的遗传机制。Thummi)。在摇蚊中，一系列实验性的扰动可以导致完全或部分轴反转(镜像双腹或双头)，这也可能自发发生。这些观察表明，早期蚊子胚胎中AP的极性非常不稳定。此外，蚊子缺乏决定果蝇(昆虫发育的关键模型)胚胎AP极性的同源异型盒基因BIYOID。我们已经建立了研究摇蚊基因表达和功能(RNA干扰、mRNA注射)的有效方法，为在蚊子模型中测试候选基因防止轴反转的能力提供了工具。这项建议的具体目的是(1)测试在其他昆虫早期AP轴规范中涉及的基因的摇蚊同源物，以了解它们防止或诱导头部或腹部镜像复制的能力，以及(2)确定这些基因如何相互调节。这些实验将导致摇蚊胚胎中AP轴规范的模型，该模型可能普遍适用于蚊子。 公共卫生相关性：摇蚊为蚊子分支提供了一种新的实验系统。对早期胚胎的功能遗传学研究是可行的，因此应该有助于了解果蝇和医学上相关的库蚊(如疟疾(按蚊)、黄热病(伊蚊)和河盲症(伊蚊)的媒介)在胚胎发育方面的差异。由于这一组早期胚胎的头到尾的极性很容易受到干扰，潜在的遗传机制可能是对抗医学相关物种的合适靶点。

DESCRIPTION (provided by applicant): Genetic circuitry of early embryos provides targets for population replacement strategies, which have important potential applications in the control of disease vectors such as mosquitoes. However, mosquito development remains poorly understood because current research in this group focuses on human disease vectors in which a tough and heavily pigmented eggshell hinders functional developmental studies. The research goal of this proposal is to elucidate the genetic mechanism that determines anterior-to-posterior (AP) polarity in embryos of the culicomorphan mosquito Chironomus riparius (syn. C. thummi). In Chironomus, a range of experimental perturbations can lead to complete or partial axis inversions (mirror image double abdomens or double heads), which may also occur spontaneously. These observations suggest that AP polarity in early mosquito embryos is very labile. Furthermore, mosquitoes lack the homeobox gene bicoid, which determines embryonic AP polarity in the fruit fly Drosophila (a key model for insect development). We have established efficient protocols for studying gene expression and function (RNA interference, mRNA injection) in Chironomus riparius, providing the tools for testing the ability of candidate genes to prevent axis inversions in a mosquito model. The specific aims of this proposal are to (1) to test Chironomus homologues of genes that have been implicated in early AP axis specification in other insects for their ability to prevent or induce mirror image duplications of the head or abdomen, and (2) to determine how these genes regulate each other. The experiments will result in a model for AP axis specification in Chironomus embryos that might be generally applicable for mosquitoes. PUBLIC HEALTH RELEVANCE: Chironomus provides a new experimental system on the mosquito branch. It is amenable to functional genetic studies in early embryos and should therefore help to understand differences in embryonic development between Drosophila and medically relevant culicomorphan mosquitoes such as the vectors of Malaria (Anopheles), Yellow fever (Aedes) and River blindness (Simulium). As head-to-tail polarity in early embryos of this group is easily perturbed, the underlying genetic mechanism could be a suitable target for combating medically relevant species.