Specification of anterioposterior polarity in the mosquito, Chironomus

描述（由申请人提供）：早期胚胎的遗传电路为种群替代策略提供了目标，这在控制疾病媒介如蚊子方面具有重要的潜在应用。然而，蚊子的发育仍然知之甚少，因为这一组目前的研究集中在人类疾病的载体，其中一个坚韧和重色素的蛋壳阻碍功能发育研究。这项研究的目的是阐明决定库蚊摇蚊胚胎中前后极性的遗传机制。C. thummi）。在摇蚊中，一系列的实验扰动可以导致完全或部分的轴反转（镜像双透镜或双头），这也可能自发发生。这些观察结果表明，AP极性在早期蚊子胚胎是非常不稳定的。此外，蚊子缺乏同源盒基因bicoid，该基因决定果蝇（昆虫发育的关键模型）中的胚胎AP极性。我们已经建立了有效的协议，研究基因表达和功能（RNA干扰，mRNA注射）在摇蚊riparius，提供的工具，用于测试候选基因的能力，以防止轴倒位的蚊子模型。该提议的具体目的是（1）测试与其他昆虫中早期AP轴特化有关的基因的摇蚊同源物，以确定其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。这些实验将导致在摇蚊胚胎AP轴规格，可能是普遍适用于蚊子的模型。

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.