Many devastating human diseases are transmitted by mosquitoes because of their requirement to blood feed for egg development. Disease-causing pathogens have adapted successfully to exploit this feature of mosquito biology for their own life cycles. Hence, the understanding of molecular mechanisms controlling egg development in these vectors is essential for devising novel methods to disrupt disease spread. We will thus decipher the hormonal genetic pathways that regulate mosquito female reproduction;the juvenile hormone regulatory cascade governing the post-eclosion development of the Aedes aegypti female fat body (FB;the tissue essential for egg development) will be investigated by means of transcriptome, bioinformatics, and RNA interference analyses. We will also decipher the differential action of the 20-hydroxyecdysone regulatory cascade in controlling genes critical for the progression of vitellogenesis in A. aegypti. We will determine cis motifs responsible for co-regulating specific patterns of FB gene expression. The newly developed mosquito GAL4-UAS genetic system will permit testing these promoters. This genetic system is also invaluable in evaluating functions of genes, identified in transcriptomic screens, by means of their mis-regulation or RNAi-depletion. Accomplishment of the goals of this comprehensive research program will significantly advance our understanding of the molecular basis of mosquito reproduction, and the resulting data will build a foundation for deciphering new targets for mosquito control.
Mosquitoes transmit many devastating human diseases because of their requirement to blood feed for egg development. Disease-causing pathogens have successfully adapted to exploit this feature of mosquito biology. The understanding of molecular mechanisms controlling egg development is thus essential for devising novel methods to disrupt disease spread. In this research project, we will elucidate hormonal genetic pathways regulating mosquito female reproduction, the knowledge of which will build a foundation for deciphering new targets for mosquito control.
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|Zhu, Jinsong; Chen, Li; Raikhel, Alexander S (2007) Distinct roles of Broad isoforms in regulation of the 20-hydroxyecdysone effector gene, Vitellogenin, in the mosquito Aedes aegypti. Mol Cell Endocrinol 267:97-105|
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|Sun, GuoQiang; Zhu, Jinsong; Chen, Li et al. (2005) Synergistic action of E74B and ecdysteroid receptor in activating a 20-hydroxyecdysone effector gene. Proc Natl Acad Sci U S A 102:15506-11|
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