Deletion of the Serotonin Receptor 7 Gene Changed the Development and Behavior of the Mosquito, Aedes aegypti

Abstract

Serotonin (5-HT) plays a vital role in many physiological processes in insects, regulating physiological activities such as growth and movement through multiple 5-HT receptors (5-HTRs), which were potential targets for some new insecticides. However, the specific function of individual 5-HTRs in Ae. aegypti is still unclear. In this study, we investigated the function of the 5-HT7A receptor during Ae. aegypti development. 5-HTR7A transcripts were detected at all stages of development by real-time PCR. The results indicated that the gene expression was highest in the limbs (p < 0.01). We also generated 5-HTR7A mutant mosquitoes using CRISPR-mediated gene editing. The mutants had an abnormal phenotype at the larval stage, including an aberrant head-to-chest ratio and decreased motor activity. The mutant pupae developed abnormally, and most died (56.67%) (p < 0.0001). Using external stimuli to larvae and pupae with abnormal phenotypes, we found the mutant G1 and G2 generations responded to external stimuli in a longer time than the wild-type (WT) mosquitoes, and most of the mutants were 2 to 3 s slower than the WTs to respond to external stimuli (p < 0.01). Due to higher mortality, mutant larvae and pupae had fewer numbers than the WTs. The egg hatching rate of mutant G1 and G2 generations was lower than that of the WTs (p < 0.01). The expression level of 5-HTR7A in the mutants decreased by about 65% compared with the control group using real-time PCR (p < 0.05). In all, the 5-HT7A receptor plays an important role in the metamorphosis, development and motor function of Aedes aegypti.

Characterization of a novel RNAi yeast insecticide that silences mosquito 5-HT1 receptor genes

“…Although larvae ingesting control yeast 48 survived, ~ 90% of those consuming the interfering RNA 5-HTR.426 yeast died in indoor laboratory trials (Table 2 ), indicating that the yeast is significantly (P < 0.001) larvicidal to A. aegypti, A. albopictus, A. gambiae, C. pipiens, and C. quinquefasciatus mosquitoes. Although deletion of the 5-HT7A receptor resulted in larvae with aberrant head-to-chest ratios and decreased motility 39 , neither phenotype was observed in 5HTR.426-treated larvae. Likewise, although disruption of the A. aegypti 5HT2B receptor resulted in reduced larval size 38 , this phenotype was not observed following the silencing of 5-HTR1 in any of the mosquito larval species.…”

“…In A. aegypti and A. gambiae , the dysfunction of 5-HTRs was reported to adversely affect adult locomotion (inhibition of flight performance) and blood-feeding behavior, identifying the 5-HTRs as potential insecticide targets for the disease vectors 10 . CRISPR-Cas9-mediated silencing of 5-HTR2B in adult A. aegypti was recently shown to inhibit growth through reduced lipid accumulation 38 , whereas the deletion of 5-HTR7A resulted in significant larval and pupal mortality 39 . More recently, inhibition of the serotonergic system in adult A. aegypti altered male phonotaxis, a behavior that’s associated with hearing impairment and has implications on mating behavior 40 .…”

Insane in the brain : How neuroparasites manipulate the insect’s brain function and behaviour

“…The role of 5HT-7 is however not clear in insects, yet seems to be highly expressed in the insects' brains and head in Tribolium castaneum (Vleugels et al 2014). A mutant 5ht-7 mosquito uncovered changes in development and reduced motility and stress response to external stimuli (Li et al 2022b) and a knockdown experiment of 5ht-7 in S. exigua, displayed immunosuppression and the involvement of these receptor in phagocytosis and nodulation (Hasan et al 2019). The same study also demonstrated that secondary metabolites from a bacterium specifically inhibit this receptor.…”