Juvenile hormone biosynthesis in mosquitoes: An update

The adult female mosquito Aedes aegypti is an excellent model to study JH biosynthesis. The genome is sequenced, molecular tools such as RNAi are available, and its JH-dependent reproductive physiology is well understood. All the genes encoding biosynthetic enzymes have been identified, comprehensive transcriptional studies have been completed, and several recombinant enzymes have been characterized. Several allatoregulatory factors are able to modify JH biosynthesis in vitro by corpora allata (CA) of adult female mosquitoes, including allatotropin (AT), allatostatin-C (AST-C), ecdysis triggering hormone (ETH) and insulin (INS). Receptors for all these allatoregulatores are expressed in the corpora allata-corpora cardiac complex (CA-CC). These different allatoregulatory factors might have modulatory effects during specific times throughout the development and gonotrophic cycle of female mosquitos. With the advent of new methods that facilitate the analysis of transcripts, enzymes and metabolites in the small CA, we were able to provide comprehensive descriptions of the mevalonic (MVA) and JH synthesis pathway by integrating information on changes in the basic components of those pathways. Our studies provide a previously unseen glimpse into the metabolomics of the MVA and juvenile hormone (JH) synthesis pathways in the CA of insects. Our results revealed remarkable dynamic changes in JH synthesis and exposed part of a complex mechanism that regulates CA activity. Principal component (PC) analysis validated that both pathways (MVAP and JH branch) are transcriptionally co-regulated as a single unit, and coordinate fashion. Metabolite studies showed that global fluctuation in the intermediate pool sizes in the MVAP and JH-branch were often inversely related. PC analyses of metabolites suggest that in female mosquitoes, there are at least 4 developmental switches that alter JH synthesis by modulating the flux at distinctive points in both pathways. The fine tuning of JH synthesis to different physiological stages in mosquito reproduction seems to occur through changes in the size of the precursor pools, rather than by changes in mRNA and enzyme capacity levels.