Wnt參與埃及斑蚊變態過程之探討

Abstract

病媒蚊傳播的寄生蟲或病毒性疾病，如瘧疾、登革熱、黃熱病…等，每年皆造成上億的病例，超過百萬人死亡。但目前針對這些傳染性疾病大多缺乏有效的疫苗，此外，有些流行地區的瘧原蟲已對抗瘧疾藥物產生抗藥性；因此，許多研究團隊開始思考藉由控制病媒蚊的傳病能力，以達到控制疾病的目的。其中，藉由生物防治的方式來達到降低病媒蚊的族群數量，被認為是一個可行的替代性策略。過去的研究已證實Wnt signaling pathway參與果蠅的胚胎發育與細胞極性調控，但在埃及斑蚊中對Wnt signaling pathway的研究卻付之闕如，因此我們亟欲探討Wnt signaling pathway於埃及斑蚊中是否在生長發育上也扮演重要角色。本實驗室過去利用RNAi的方式，分別抑制埃及斑蚊中Frizzle2 (Wnt的受體)與Wnt740 (Fz的配體)的表現，發現吸血後的母蚊相較於對照組，其產下的卵數大幅減少。此外我們也發現，在蛹期抑制AaWnt740的表現時，其羽化的比例也明顯降低。並且在我們的實驗當中，觀察到母蚊在羽化過程中無法完全羽化(Incomplete eclosion)。我們更進一步證明，此種羽化不完全的現象是由非典型的Wnt signaling pathway，即planar cell polarity (PCP) pathway所調控。本研究結果將有助於未來發展新的病媒控制策略，以控制病媒傳染病之傳播。

Mosquito-borne diseases are the most devastating agents for human beings, such as malaria, dengue fever, West Nile fever…etc. The WHO reported that some 2.5 billion people are now at risk and more than a million people are killed by mosquito-borne diseases annually. Up to now, no effective vaccine or drug has been developed for most of these diseases. Therefore, any possible avenue for developing novel control strategies against mosquito-borne diseases is urgently needed. Wnt signaling pathway is shown to be participated in the embryonic development and cell polarity in Drosophila. However, the functions of Wnt signaling remain largely unknown in the mosquito. In this study, we attempt to characterize the role of Wnt signaling in the yellow fever mosquito, Aedes aegypti. Our previous results showed that silencing of Frizzl2 (the Wnt signaling pathway receptor) and Wnt (the Wnt signaling pathway ligand) resulted in the reduction of eggs production. Interestingly, silencing of Wnt reduced the eclosion rate in the mosquito. Therefore, we would like to elucidate the role of Wnt in the regulation of mosquito morphogenesis, which will be crucial for the development of novel vector control strategy. Our results showed that Wnt was highly expressed in the mosquito pupal stage in terms of transcriptional level. Intriguingly, we observed that silencing of Wnt740 exhibited an incomplete eclosion phenotype in the mosquito pupae. Furthermore, we demonstrated that this phenotype was regulated by planar cell polarity (PCP) pathway, the non-canonical Wnt signaling pathway. Information gathered in this study will pave the way toward the establishment of efficient strategies for vector control by using molecular engineering approaches.