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 to 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. The rate of CA activity is, in turn, regulated by allato-regulatory peptides that exert either allatostatic (inhibitory) or allatotropic (stimulatory) activities. During the first three years of this project we have described that allatotropin (AT) stimulates and allatostatin-C (AS-C) inhibits JH synthesis, that nutrients accumulated during the larval stages regulate CA activity, and also performed the first genomic analysis of an insect endocrine gland. Based on this work we propose that AT and AS released by the brain are essential for the activation and modulation of JH synthesis in adult female mosquitoes. The synthesis and release of these peptides is connected to nutritional signals. JH is therefore an important part of a transduction mechanism that connects changes in the nutritional status with activation of specific physiological events during reproduction. The goal of this project is to understand how peptides regulate the synthesis of JH in mosquitoes. The ultimate aim of this project is to reveal how changes in the mosquito's nutritional status are assessed and how this information is transduced to the CA. In order to test this model, in this application we propose to: 1. Investigate the mechanisms of control of JH synthesis by AT and AS-C. 2. Study the nutritional regulation of synthesis and release of AT and AS-C in the brain. Understanding the molecular basis of the physiological action of neuro-peptides will guide us in designing new and affordable agents for vector control. ? ?
| 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 |
| Villalobos-Sambucaro, María José; Lorenzo-Figueiras, Alicia Nieves; Riccillo, Fernando Luis et al. (2015) Allatotropin modulates myostimulatory and cardioacceleratory activities in Rhodnius prolixus (Stal). PLoS One 10:e0124131 |
| Nouzova, Marcela; Rivera-Perez, Crisalejandra; Noriega, Fernando G (2015) Allatostatin-C reversibly blocks the transport of citrate out of the mitochondria and inhibits juvenile hormone synthesis in mosquitoes. Insect Biochem Mol Biol 57:20-6 |
| Mesquita, Rafael D; Vionette-Amaral, Raquel J; Lowenberger, Carl et al. (2015) Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection. Proc Natl Acad Sci U S A 112:14936-41 |
| 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 |
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