Identification and characterization of a mosquito-specific eggshell organizing factor in Aedes aegypti mosquitoes

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Mosquito-borne diseases are responsible for several million human deaths annually around the world.One approach to controlling mosquito populations is to disrupt molecular processes or antagonize novel metabolic targets required for the production of viable eggs.To this end, we focused our efforts on identifying proteins required for completion of embryonic development that are mosquito selective and represent potential targets for vector control.We performed bioinformatic analyses to identify putative protein-coding sequences that are specific to mosquito genomes.Systematic RNA interference (RNAi) screening of 40 mosquito-specific genes was performed by injecting double-stranded RNA (dsRNA) into female Aedes aegypti mosquitoes.This experimental approach led to the identification of eggshell organizing factor 1 (EOF1, AAEL012336), which plays an essential role in the formation and melanization of the eggshell.Eggs deposited by EOF1-deficient mosquitoes have nonmelanized fragile eggshells, and all embryos are nonviable.Scanning electron microscopy (SEM) analysis identified that exochorionic eggshell structures are strongly affected in EOF1-deficient mosquitoes.EOF1 is a potential novel target, to our knowledge, for exploring the identification and development of mosquito-selective and biosafe small-molecule inhibitors. Author summaryMosquito-borne pathogens infect millions of people worldwide, and the rise in insecticide resistance is exacerbating this problem.A new generation of environmentally safe insecticides will be essential to control insecticide-resistant mosquitoes.One potential route to such novel insecticide targets is the identification of proteins specifically needed for mosquito reproduction.Female mosquitoes feed on blood to produce eggs, which are covered with an eggshell; using RNA interference screening of mosquito-specific genes in Aedes

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