Mosquito-transmitted parasitic diseases are among the major causes of mortality and morbidity in the world. Recent dramatic increases in the incidence of mosquito-borne diseases, like malaria and dengue fever, and the wide-spread resistance of mosquitoes to insecticides underscores the need for new approaches for insect control based on mosquito-specific agents. The discovery of such mosquito-specific control agents depends on basic research on the biology of mosquitoes. Juvenile hormone (JH) is a major hormonal regulator in insects. In the female mosquito, JH signals the completion of the ecdysis to the adult stage, and initiates reproductive processes. JH titer is essentially determined by the rate at which the corpora allata (CA) synthesizes JH. Our research, using an integrative approach that combines experiments at the organismal, cellular and molecular level, is revealing that mosquito regulation of JH activity has unique features that are related to the adaptation to blood-feeding and the cyclic regulation of ovarian development. We have described that the CA of the female mosquito alternates between periods of high and low biosynthetic activity that are linked to developmental programs and nutritional signals. We have identified neuropeptides that stimulate or inhibit JH synthesis and have characterized their receptors. We have performed the first genomic analysis of an insect endocrine gland and studied the expression of most of the JH biosynthetic enzymes. We have also described that nutrients accumulated during the larval stages regulate CA activity and developed a unique model of nutritionally deficient mosquitoes that do not synthesize JH. The goal of this project is to understand the role and mechanism of action of the different factors that control CA activity (allatoregulatory factors). We also seek to identify the rate limiting steps and regulatory points of JH synthesis. To accomplish these goals, we will focus on two key stages: 1) the activation of JH synthesis in the newly emerged adult female and 2) the inactivation of the CA after blood- feeding. These two stages are critical moments in the reproductive maturation of mosquitoes and make excellent experimental models that are also relevant for disease control. These areas of research should identify targets for designing new, specific and affordable chemical strategies suitable for mosquito control in developing countries.

Public Health Relevance

Mosquito-borne diseases are major public health problems in developing countries. The discovery of mosquito-specific control agents depends on basic research on the biology of mosquitoes. Juvenile hormone (JH) is a major hormonal regulator that controls development and reproduction in mosquitoes and this research aims to understand the unique features of JH synthesis in mosquito and identify targets for designing new, specific and affordable chemical strategies suitable for mosquito depletion or incapacitation in endemic areas.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IDM-A (02))
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Costero, Adriana
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Florida International University
Schools of Arts and Sciences
United States
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Nouzova, Marcela; Michalkova, Veronika; Hernández-Martínez, Salvador et al. (2018) JH biosynthesis and hemolymph titers in adult male Aedes aegypti mosquitoes. Insect Biochem Mol Biol 95:10-16
Rivera-Pérez, Crisalejandra; Clifton, Mark E; Noriega, Fernando G (2017) How micronutrients influence the physiology of mosquitoes. Curr Opin Insect Sci 23:112-117
Martínez-Rincón, Raúl O; Rivera-Pérez, Crisalejandra; Diambra, Luis et al. (2017) Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations. PLoS One 12:e0171516
Hernández-Martínez, Salvador; Sánchez-Zavaleta, Minerva; Brito, Kevin et al. (2017) Allatotropin: A pleiotropic neuropeptide that elicits mosquito immune responses. PLoS One 12:e0175759
Villalobos-Sambucaro, María José; Diambra, Luis Anibal; Noriega, Fernando Gabriel et al. (2016) Allatostatin-C antagonizes the synergistic myostimulatory effect of allatotropin and serotonin in Rhodnius prolixus (Stal). Gen Comp Endocrinol 233:1-7
Ramirez, Cesar E; Nouzova, Marcela; Benigni, Paolo et al. (2016) Fast, ultra-trace detection of juvenile hormone III from mosquitoes using mass spectrometry. Talanta 159:371-8
Rivera-Perez, Crisalejandra; Nyati, Pratik; Noriega, Fernando G (2015) A corpora allata farnesyl diphosphate synthase in mosquitoes displaying a metal ion dependent substrate specificity. Insect Biochem Mol Biol 64:44-50
Hernández-Martínez, Salvador; Rivera-Perez, Crisalejandra; Nouzova, Marcela et al. (2015) Coordinated changes in JH biosynthesis and JH hemolymph titers in Aedes aegypti mosquitoes. J Insect Physiol 72:22-27
Wen, Di; Rivera-Perez, Crisalejandra; Abdou, Mohamed et al. (2015) Methyl farnesoate plays a dual role in regulating Drosophila metamorphosis. PLoS Genet 11:e1005038
Nyati, Pratik; Rivera-Perez, Crisalejandra; Noriega, Fernando G (2015) Negative Feedbacks by Isoprenoids on a Mevalonate Kinase Expressed in the Corpora Allata of Mosquitoes. PLoS One 10:e0143107

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