Mosquitoes are well recognized as the most important arthropod vectors of disease-causing pathogens. This is because most species are anautogenous and must feed on the blood of a human or other vertebrate to produce eggs. Multiple cycles of blood feeding and egg development in turn favors frequent contacts with hosts, which makes mosquitoes ideal vectors for pathogen transmission. Since disruption of egg production also disables pathogen transmission, understanding the reproduction of anautogenous mosquitoes is an important area of study. This application is a renewal request to continue our work on how egg development is regulated. Our current award focuses on Aedes aegypti, which is the species we best understand how egg maturation is regulated. Our studies indicate that two neurohormones, ovary ecdysteroidogenic hormone (OEH) and insulin-like peptides (ILPs) from the brain, function as key regulators of the egg development process. However, we also have found that OEH but not ILPs is also able to stimulate egg formation in the absence of blood feeding. To advance these results, we need to better understand OEH function in Ae. aegypti, other anautogenous species like Anopheles gambiae, and non-blood feeding autogenous species like.
Our Specific Aims to meet these goals are: 1. Characterize OEH mediated nutrient mobilization and egg maturation in Ae. aegypti. 2. Assess the roles of OEH and ILPs in egg development of An. gambiae and O. atropalpus. 3. Assess the effects of OEH, ILP3, rapamycin and insulin receptor inhibitor PQIP in disabling mosquito reproduction. Expected outcomes of our work will include an enhanced understanding of how egg production is regulated in anautogenous and autogenous species. Our study will also provide important insights into how egg development can be disabled.

Public Health Relevance

Mosquitoes are the most important arthropod vectors of disease-causing pathogens. Our work will help us understand the mechanisms that control blood feeding and egg production in mosquitoes, which are critical issues in transmission of disease-causing parasites. This will provide the foundation for development of new approaches for controlling mosquito reproduction and reducing disease transmission.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Vector Biology Study Section (VB)
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Costero-Saint Denis, Adriana
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University of Georgia
Earth Sciences/Resources
United States
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Nuss, Andrew B; Brown, Mark R (2018) Isolation of an insulin-like peptide from the Asian malaria mosquito, Anopheles stephensi, that acts as a steroidogenic gonadotropin across diverse mosquito taxa. Gen Comp Endocrinol 258:140-148
McKinney, David A; Strand, Michael R; Brown, Mark R (2017) Evaluation of ecdysteroid antisera for a competitive enzyme immunoassay and extraction procedures for the measurement of mosquito ecdysteroids. Gen Comp Endocrinol 253:60-69
McKinney, David A; Eum, Jai-Hoon; Dhara, Animesh et al. (2016) Calcium influx enhances neuropeptide activation of ecdysteroid hormone production by mosquito ovaries. Insect Biochem Mol Biol 70:160-9
Strand, M R; Brown, M R; Vogel, K J (2016) Mosquito Peptide Hormones: Diversity, Production, and Function. Adv In Insect Phys 51:145-188
Vogel, Kevin J; Brown, Mark R; Strand, Michael R (2015) Ovary ecdysteroidogenic hormone requires a receptor tyrosine kinase to activate egg formation in the mosquito Aedes aegypti. Proc Natl Acad Sci U S A 112:5057-62
Gulia-Nuss, Monika; Elliot, Anne; Brown, Mark R et al. (2015) Multiple factors contribute to anautogenous reproduction by the mosquito Aedes aegypti. J Insect Physiol 82:8-16
Coon, Kerri L; Vogel, Kevin J; Brown, Mark R et al. (2014) Mosquitoes rely on their gut microbiota for development. Mol Ecol 23:2727-39
Hillyer, Julián F; Strand, Michael R (2014) Mosquito hemocyte-mediated immune responses. Curr Opin Insect Sci 3:14-21
Vogel, Kevin J; Brown, Mark R; Strand, Michael R (2013) Phylogenetic investigation of Peptide hormone and growth factor receptors in five dipteran genomes. Front Endocrinol (Lausanne) 4:193
Dhara, Animesh; Eum, Jai-Hoon; Robertson, Anne et al. (2013) Ovary ecdysteroidogenic hormone functions independently of the insulin receptor in the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol 43:1100-8

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