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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI036959-17A1
Application #
8291561
Study Section
Special Emphasis Panel (ZRG1-IDM-V (02))
Program Officer
Costero, Adriana
Project Start
1995-07-01
Project End
2017-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
17
Fiscal Year
2012
Total Cost
$560,350
Indirect Cost
$187,463
Name
University of California Riverside
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
Zou, Zhen; Saha, Tusar T; Roy, Sourav et al. (2013) Juvenile hormone and its receptor, methoprene-tolerant, control the dynamics of mosquito gene expression. Proc Natl Acad Sci U S A 110:E2173-81
Lucas, Keira; Raikhel, Alexander S (2013) Insect microRNAs: biogenesis, expression profiling and biological functions. Insect Biochem Mol Biol 43:24-38
Cruz, Josefa; Mane-Padros, Daniel; Zou, Zhen et al. (2012) Distinct roles of isoforms of the heme-liganded nuclear receptor E75, an insect ortholog of the vertebrate Rev-erb, in mosquito reproduction. Mol Cell Endocrinol 349:262-71
Kokoza, Vladimir A; Raikhel, Alexander S (2011) Targeted gene expression in the transgenic Aedes aegypti using the binary Gal4-UAS system. Insect Biochem Mol Biol 41:637-44
Cruz, Josefa; Sieglaff, Douglas H; Arensburger, Peter et al. (2009) Nuclear receptors in the mosquito Aedes aegypti: annotation, hormonal regulation and expression profiling. FEBS J 276:1233-54
Bian, Guowu; Raikhel, Alexander S; Zhu, Jinsong (2008) Characterization of a juvenile hormone-regulated chymotrypsin-like serine protease gene in Aedes aegypti mosquito. Insect Biochem Mol Biol 38:190-200
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
Zhu, Jinsong; Chen, Li; Sun, Guoqiang et al. (2006) The competence factor beta Ftz-F1 potentiates ecdysone receptor activity via recruiting a p160/SRC coactivator. Mol Cell Biol 26:9402-12
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
Chen, L; Zhu, J; Sun, G et al. (2004) The early gene Broad is involved in the ecdysteroid hierarchy governing vitellogenesis of the mosquito Aedes aegypti. J Mol Endocrinol 33:743-61

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