Search bioRxiv⌕ Search

Biology subjects

Duvall, L. B.

Publications and source records attributed to Duvall, L. B..

11 recordsLinked to original sources

Aedes aegypti from a Population Co-occurring with Aedes albopictus Show Species-Selective Premating and Postmating Resistance to Reproductive Interference

BackgroundA female Aedes aegypti mosquito typically mates only once, receiving all of the reproductive materials required for her lifetime from a single male. During mating, males transfer chemical signals that permanently suppress female receptivity to subsequent mating attempts. Successful mating can be disrupted by satyrization, a form of interspecific reproductive interference in which Aedes albopictus males inseminate Aedes aegypti females without producing viable offspring, effectively rendering them sterile. Aedes aegypti populations from areas where both species co-occur can develop resistance to satyrization, which may arise through premating mechanisms including altered mating interactions and/or postmating mechanisms including reduced female sensitivity to male-derived chemical compounds. Methodology/Principal FindingsWe compared two Aedes aegypti strains derived from field collections in Lee County, Florida: one from a site where Aedes albopictus is established (Fort Myers) and one from a site with no known history of Aedes albopictus co-occurrence (Upper Captiva Island). Using laboratory mating assays, fluorescent dye transfer experiments, and male reproductive homogenate injections, we show that females from the co-occurring population exhibit reduced susceptibility to satyrization. This resistance is associated with two distinct mechanisms: reduced physical interactions with heterospecific males and reduced physiological sensitivity to Aedes albopictus homogenate following injection. Notably, co-occurring females retain sensitivity to signals from conspecific males, indicating that resistance mechanisms are species-selective rather than a generalized reduction in mating responsiveness. ConclusionsAedes aegypti females from a population co-occurring with Aedes albopictus show reduced susceptibility to satyrization under laboratory conditions, mediated by both premating and postmating mechanisms. The species selectivity of these responses suggests that co-occurring populations can discriminate between conspecific and heterospecific signals. Understanding how this discrimination is achieved and how it varies across populations will be important for interpreting interspecific mating dynamics and for evaluating vector control strategies that depend on mating interference, including sterile male release programs.

animal behavior and cognition↗

A Signaling Hub in the Mosquito Rectum Coordinates Reproductive Investment After Blood Feeding

After a blood meal, female Aedes aegypti mosquitoes suppress host-seeking while converting ingested nutrients into yolk protein for egg development. Neuropeptide Y-like Receptor 7 (NPYLR7) is required for this behavioral switch, but its physiological role and sites of action were unknown. We identify a specialized, non-neuronal population of npylr7-expressing cells in the rectal pads of the mosquito hindgut. While this tissue is associated with fluid and ion balance, npylr7 mutants maintain fluid regulation but show impaired oocyte provisioning. These cells display neuroendocrine features, including calcium responses to the NPYLR7 ligand RYamide and amino acids, as well as expression of neurotransmitter synthesis and vesicle release machinery. Vesicle recruitment occurs in these cells post-blood meal in wild-type, but not npylr7 mutants. Our findings reveal an unexpected role for NPYLR7 in a rectal cell population senses nutritional cues and communicates with the nervous system to regulate reproductive physiology, paralleling gut-brain circuits in mammals.

neuroscience↗

Post-biting behavioral reprogramming underlies reproductive efficiency in Aedes aegypti mosquitoes

The global spread and increasing populations of disease vector mosquitoes expose hundreds of millions of people to mosquito-borne illnesses each year. Female Aedes aegypti mosquitoes, global vectors of dengue, require protein from host blood to support egg development and undergo repeated cycles of blood-feeding and egg-laying. After biting, females temporarily alter their behavioral state and suppress host-seeking while using blood-derived nutrients to develop eggs. Host-seeking suppression ends once eggs are laid. While this period has generally been thought of as one of behavioral inactivity, we reveal that it instead reflects behavioral reprogramming, during which females transition from post-blood-meal inactivity into active searching for egglaying sites. Females with mature eggs show a distinct behavioral state characterized by increased locomotor activity and a shift in circadian behavioral timing, leading to nocturnal humidity-seeking and egg-laying in an otherwise diurnal species. We show that the circadian clock gene cycle is critical for regulating this transition; its absence disrupts the timing of oviposition behaviors, leading to poor site selection and reduced predicted offspring survival. These findings suggest that during egg development, circadian clock-dependent behavioral reprogramming triggers nocturnal hyperactivity and oviposition site search, an essential process for mosquito reproduction and population viability.

neuroscience↗

Behavioral heterogeneity in host-seeking and post-feedingsuppression among disease vector mosquitoes

Female mosquitoes seek out vertebrate hosts and consume their blood to obtain nutrients necessary for egg production, but host preference and host-seeking strategies differ markedly across species. These behaviors are also modulated by internal physiological states, such as the suppression of host-seeking after a full blood meal, a phenomenon that varies in timing and duration across mosquito species. We established a behavior monitoring and classification pipeline to systematically compare baseline host-seeking behavior and post-blood meal suppression in Aedes, Anopheles, and Culex mosquitoes. We found distinct behavioral signatures and notable interspecific differences in the onset and duration of host-seeking suppression. While Aedes and Anopheles host-seeking behaviors have been extensively studied in laboratory settings, comparable behavioral data for Culex have been limited, making direct comparisons across all three genera difficult. Our findings establish a unified behavioral framework for mosquito host-seeking across key vector species, providing insight into the ecological and physiological factors that shape host interaction and offering a foundation for improved modeling of disease transmission and vector control.

animal behavior and cognition↗

Circadian modulation of mosquito host-seeking persistence by Pigment-Dispersing Factor impacts daily biting patterns

Daily rhythms in mosquito attraction to humans are thought to drive biting patterns and contribute to disease transmission dynamics. Behavioral rhythms in many insects are controlled by specialized clock cells in the brain that are coordinated by the neuropeptide Pigment-Dispersing Factor (PDF). We show that female Aedes aegypti mosquitoes with genetically disrupted PDF display altered daily behavioral timing with reduced locomotor activity and biting in the morning. Using an automated behavioral tracking system, we also report that mosquitoes exhibit daily modulation of response persistence to the host cue carbon dioxide and loss of PDF alters this pattern. These findings indicate that PDF regulates temporal features of host-seeking behavior that promote biting success at specific times of day and may underlie blood feeding patterns observed in the field.

neuroscience↗

Temperature and photoperiod differentially impact maternal phenotypes in diapause egg-laying Aedes albopictus mosquitoes

BackgroundAedes albopictus (Skuse 1894) mosquitoes can transmit deadly arboviruses and are globally invasive due to their ability to survive in both tropical and temperate climates. Although adults cannot survive harsh winters, females are capable of anticipating seasonal change and producing overwintering diapause (DP) eggs that remain in a state of arrested development over the winter and hatch when favorable conditions return in the spring. Previous work has shown that shortening photoperiod (day length) alone is sufficient for DP induction. While decreasing temperatures can facilitate DP entry, temperature signals alone are not sufficient to induce DP. Methodology/Principal FindingsTo identify maternal phenotypes predictive of DP egg production, we characterized aspects of maternal physiology and behavior to identify those that correlate with DP egg production and changes in photoperiod, versus changes in temperature. Neither changes in temperature nor photoperiod impacted protein preference, blood meal consumption, or total number of eggs produced per female. Egg retention and oviposition timing were influenced by temperature, independent of DP egg production. However, females housed under short photoperiod conditions showed increased starvation resistance, despite showing similar levels of locomotor activity and internal stores of triacylglycerols, glucose, glycogen, and trehalose compared to females housed in long photoperiods. Conclusions/SignificanceThese results suggest that temperature and photoperiod differentially affect maternal phenotypes and identify starvation resistance as a maternal phenotype that is influenced by photoperiod and can be used to predict DP egg status. AUTHOR SUMMARYAedes albopictus mosquitoes can survive in temperate climates because females are able to detect changes in temperature and day length in the autumn to produce "diapause" eggs that are provisioned with extra nutrients to survive harsh winters by remaining in a state of arrest and hatching in the spring. Although temperature and day length normally change in concert with each other throughout the year, studies have shown that day length is the most important cue used by female mosquitoes to initiate diapause egg production. In this study, the authors examined aspects of feeding and reproduction to determine which of these correlated with day length. Many aspects of reproduction were influenced by temperature; however, housing female mosquitoes under autumn-like short day conditions led to increased starvation resistance. Surprisingly these females survive longer even though they do not appear to expend less energy compared to females housed in spring-like long day conditions at the same temperature. This suggests that the mosquito mothers undergo changes in their metabolism that can be used predict whether she will produce eggs that can survive the winter. This new knowledge may lead to new targets to disrupt seasonal reproduction in mosquitoes and limit the parts of the world where they can survive.

physiology↗

Next Generation Neuropeptide Y Receptor Small Molecule Agonists Inhibit Mosquito Biting Behavior

Female Aedes aegypti mosquitoes can spread disease-causing pathogens when they bite humans to obtain blood nutrients required for egg production. Following a complete blood meal, host-seeking is suppressed until eggs are laid. Neuropeptide Y-like Receptor 7 (NPYLR7) plays a role in endogenous host-seeking suppression and previous work identified small molecule NPYLR7 agonists that suppress host-seeking and blood feeding when fed to mosquitoes at high micromolar doses. Using structure activity relationship analysis and structure-guided design we synthesized 128 compounds with similarity to known NPYLR7 agonists. Although in vitro potency (EC50) was not strictly predictive of in vivo effect, we identified 3 compounds that suppressed blood feeding from a live host when fed to mosquitoes at a 1 M dose, a 100-fold improvement over the original reference compound. Exogenous activation of NPYLR7 represents an innovative vector control strategy to block mosquito biting behavior and prevent mosquito/human host interactions that lead to pathogen transmission.

pharmacology and toxicology↗

Sex peptide receptor is not required for refractoriness to remating or induction of egg laying in Aedes aegypti

Across diverse insect taxa, the behavior and physiology of females dramatically changes after mating - processes largely triggered by the transfer of seminal proteins from their mates. In the vinegar fly Drosophila melanogaster, the seminal protein sex peptide (SP) decreases the likelihood of female flies remating and causes additional behavioral and physiological changes that promote fertility including increasing egg production. Although SP is only found in the Drosophila genus, its receptor, sex peptide receptor (SPR), is the widely-conserved myoinhibitory peptide (MIP) receptor. To test the functional role of SPR in mediating post-mating responses in a non-Drosophila dipteran, we generated two independent Spr-knockout alleles in the yellow fever mosquito Aedes aegypti. Although SPR is needed for post-mating responses in Drosophila and the cotton bollworm Helicoverpa armigera, Spr mutant Ae. aegypti show completely normal post-mating decreases in remating propensity and increases in egg laying. In addition, injection of synthetic SP or accessory gland homogenate from D. melanogaster into virgin female mosquitoes did not elicit these post-mating responses. Our results indicate that Spr is not required for these canonical post-mating responses in Ae. aegypti, indicating that unknown signaling pathways are likely responsible for these behavioral switches in this disease vector.

genetics↗

Novel small molecule agonists of an Aedes aegypti neuropeptide Y receptor block mosquito biting behavior

Female Aedes aegypti mosquitoes bite humans to obtain a blood-meal to develop their eggs. Remarkably, strong attraction to humans is suppressed for several days after the blood-meal by an unknown mechanism. We investigated a role for neuropeptide Y (NPY)-related signaling in this long-term behavioral suppression, and discovered that drugs targeting human NPY receptors modulate mosquito host-seeking behavior. In a screen of all 49 predicted Ae. aegypti peptide receptors, we identified NPY-like receptor 7 (NPYLR7) as the sole target of these human drugs. To obtain small molecule agonists selective for NPYLR7, we carried out a high-throughput cell-based assay of 265,211 compounds, and isolated 6 highly selective NPYLR7 agonists that inhibit mosquito attraction to humans. NPYLR7 CRISPR-Cas9 null mutants are defective in behavioral suppression, and resistant to these drugs. Finally, we show that these drugs are capable of inhibiting biting and blood-feeding on a live host, suggesting a novel approach to control infectious disease transmission by controlling mosquito behavior.

neuroscience↗

A natural variant and an engineered mutation in a GPCR promote DEET resistance in C. elegans

DEET (N,N-diethyl-meta-toluamide) is a synthetic chemical, identified by the United States Department of Agriculture in 1946 in a screen for repellents to protect soldiers from mosquito-borne diseases1,2. Since its discovery, DEET has become the worlds most widely used arthropod repellent3, and is effective against invertebrates separated by millions of years of evolution, including biting flies4, honeybees5, ticks6, and land leeches4,7. In insects, DEET acts on the olfactory system5,8-14 and requires the olfactory receptor co-receptor orco9,11-13, but its specific mechanism of action remains controversial. Here we show that the nematode Caenorhabditis elegans is sensitive to DEET, and use this genetically-tractable animal to study its mechanism of action. We found that DEET is not a volatile repellent, but interferes selectively with chemotaxis to a variety of attractant and repellent molecules. DEET increases pause lengths to disrupt chemotaxis to some odours but not others. In a forward genetic screen for DEET-resistant animals, we identified a single G protein-coupled receptor, str-217, which is expressed in a single pair of DEET-responsive chemosensory neurons, ADL. Misexpression of str-217 in another chemosensory neuron conferred strong responses to DEET. Both engineered str-217 mutants and a wild isolate of C. elegans carrying a deletion in str-217 are DEET-resistant. We found that DEET can interfere with behaviour by inducing an increase in average pause length during locomotion, and show that this increase in pausing requires both str-217 and ADL neurons. Finally, we demonstrated that ADL neurons are activated by DEET and that optogenetic activation of ADL increased average pause length. This is consistent with the \"confusant\" hypothesis, in which DEET is not a simple repellent but modulates multiple olfactory pathways to scramble behavioural responses12,13. Our results suggest a consistent motif for the effectiveness of DEET across widely divergent taxa: an effect on multiple chemosensory neurons to disrupt the pairing between odorant stimulus and behavioural response.

neuroscience↗

A Neuropeptide Signaling System That Rapidly Enforces Paternity In The Aedes aegypti Mosquito

Female Dengue and Zika vector mosquitoes (Aedes aegypti) generally mate once, with sperm from this male fertilizing all eggs produced in her lifetime. Here we implicate HP-I, an Aedes- and male-specific neuropeptide transferred to females, and its cognate receptor in the female, NPYLR1, in rapid enforcement of paternity. HP-I mutant males were ineffective in enforcing paternity when a second male was given access to the female within 1 hour. NPYLR1 mutant females produced mixed paternity offspring at high frequency. Synthetic HP-I injected into wild-type virgins reduced successful matings, but had no effect on NPYLR1 mutant females. Asian tiger mosquito (Ae. albopictus) HP-I potently activated Ae. aegypti NPYLR1. Invasive Ae. albopictus males are known to copulate with and sterilize Ae. aegypti females, and cross-species transfer of HP-I may contribute to this phenomenon. This neuropeptide system promotes rapid paternity enforcement within Ae. aegypti, but may promote local extinction in areas where they compete with Ae. albopictus.\n\nOne Sentence SummaryAedes-specific peptide rapidly enforces paternity\n\nTextAe. aegypti females typically mate only once with one male in their lifetime, a behavior known as \"monandry\" (1). This single mating event provisions the female with sufficient sperm to fertilize the >500 eggs she will produce during her [~]4-6 week lifespan in the laboratory (2). Successful mating is capable of inducing lifetime refractoriness to subsequent insemination by other males, enforcing the paternity of the first male (3-5). In other species, males use diverse strategies to assure the paternity of their offspring, for instance physical barriers such as mating plugs found in mice (6) and Anopheline mosquitoes (7), and anti-aphrodisiac pheromones used by Drosophila melanogaster males to tag female flies as non-virgin (8). Another widely used strategy in insects is the transfer of biologically active male seminal proteins, produced by the male accessory gland and secreted into the ejaculatory duct along with sperm during insemination, to affect the sexual receptivity of the female (3, 9-13). Perhaps the best-characterized male seminal fluid protein in insects is the Drosophila fly sex peptide (11), which acts on the sex peptide receptor in the female to suppress receptivity and trigger egg production (12). Drosophila sex peptide receptor mutant females will readily remate with multiple males, and wild-type females that mate with sex peptide mutant males remain sexually receptive.

neuroscience↗