Biology subjects

Xu, Y. Y.

Publications and source records attributed to Xu, Y. Y..

6 recordsLinked to original sources

bioRxiv2026

The sex determination gene doublesex is essential for female-specific flight and hearing properties in Aedes aegypti mosquitoes

The acoustic communication system supporting reproduction in disease-transmitting mosquitoes is sexually dimorphic, from the sounds that mosquitoes make to the properties of their flagellar ears. The molecular mechanisms shaping these dimorphisms, however, remain unclear. Here, we explored the contributions of the female-specific isoform of the sex determination gene doublesex (dsxF) in specifying female-unique properties in the acoustic communication system of Aedes aegypti mosquitoes. CRISPR-Cas9 based generation of a novel dsxF knockout line found that dsxF mutant females were flightless due to lack of expression of a female-specific myosin gene, myo-fem, in the thorax. We found that DsxF directly binds to four different enhancer sites of myo-fem to promote gene expression. We observed that dsxF female ears exhibited intersex neuroanatomical characteristics and contained a more extensive auditory efferent network than control females. At the peripheral hearing function level, dsxF female ears displayed intersex tuning frequencies associated with increased expression of hearing genes in dsxF female ears compared to control females. We identified three hearing genes transcriptionally inhibited by DsxF via direct binding. DsxF is a bifunctional transcription factor, activating female-specific gene expression in thoraces whilst repressing male-biased gene expression in ears to coordinate female-unique features across sensory and motor systems.

neuroscience↗

bioRxiv2026

The sex determination gene fruitless is essential for male Aedes aegypti mosquito swarming and attraction to female flight sounds

Aggregating male mosquitoes locate females by showing strong and innate attraction to female flight sounds, with these behaviors forming the basis of mating in the worlds deadliest animal. In contrast, females do not show aggregation or sound attraction behaviors. Despite being documented for almost a century, the molecular underpinnings of these behavioral dimorphisms remain unknown. Here, we found that by disrupting the male-specific isoform of the key sex determination gene fruitless (referred to as fruM) in Aedes aegypti, mutant males behave like females. fruM mutant males show complete abolition of aggregation and sound attraction behaviors, resulting in failure to locate females for mating. We identified strong fruitless expression in control male ears, with the loss of FruM severely disrupting mutant male ability to amplify female flight sounds compared to control males. fruM mutant male ears propagate frequency-specific, sound-evoked electrical signals at about one-sixth the magnitude of control males, significantly reducing the amount of auditory information relayed to the brain. fruitless thus plays a significant role in determining proper male peripheral hearing function, which enables male hearing behaviors essential for mating. Transcriptomic analyses of mosquito ears enabled identification of essential hearing genes under the transcriptional influence of FruM. We propose that FruM fine-tunes the masculinization of mosquito ears through shaping male-specific hearing cellular machineries that support male attraction to female flight sounds. We conclude that FruM is the master regulator of male-specific reproductive behaviors in mosquitoes and propose fruitless, as well as fruitless-dependent genes, as novel targets for control strategies. HighlightsO_LIFruM is the master regulator of male swarming and attraction to female flight sounds C_LIO_LIFruM in male ears is essential for male amplification of female flight sounds C_LIO_LIFruM in male ears modulates sound-evoked electrical signal propagation to the brain C_LIO_LIFruM regulates essential hearing gene expression C_LI

neuroscience↗

bioRxiv2025

Controlling malaria mosquito reproduction via the octopamine beta2 receptor

Mosquito reproduction in a broad sense involves multiple steps from acoustic recognition of mating partners to egg hatching. We show that the octopamine receptor AgOct{beta}2R controls different aspects of this process in a sexually dimorphic manner. AgOct{beta}2R knockout males present auditory defects that impair their ability to inseminate females, whilst knockout females are sterile. These phenotypes suggest AgOct{beta}2R as a target to impair mosquito reproduction at multiple levels. We test the reproductive effects of the insecticide amitraz, an AgOct{beta}2R agonist, showing that amitraz exposure reduces insemination in the lab but not in the field and has no effects on female sterility, excluding its applicability as a mating disruptor. Pharmacological assays reveal that AgOct{beta}2R sensitivity to amitraz is reduced compared to other arthropods, but its responses can be altered by modifying residues in the binding pocket. Together, our results establish AgOct{beta}2R as a promising target to disrupt mosquito reproduction but emphasize the necessity of developing new tools to exploit this approach.

neuroscience↗

bioRxiv2025

Using a female-specific isoform of doublesex to explore male-specific hearing in mosquitoes

Animal reproduction relies on elaborate divisions of labour and multiple dimorphisms between the sexes. Primary dimorphisms affect core elements of reproduction, secondary dimorphisms affect more indirect traits, including complex behaviours. In disease-transmitting mosquitoes, males locate females acoustically prior to copulation (phonotaxis). No comparable acoustic behaviour is known for females. As a result, the males ears - and hearing performance - have evolved to become substantially more complex. Sex-specific hearing in mosquitoes is in part controlled by the doublesex (dsx) gene. Intriguingly, dsx forms a linker between primary and secondary dimorphisms: spermatogenesis and ear morphogenesis share considerable molecular overlap and both depend on dsx expression patterns. We have combined transcriptomics with functional-anatomical analyses to dissect dsx-dependent hearing in the malaria mosquito Anopheles gambiae. By cross-linking our auditory findings to the genetic bases of spermatogenesis we advance the molecular understanding of sex-specific hearing mechanisms in insects, highlighting the special roles of ciliary factors therein. HighlightsO_LIDisruption of the female-specific exon of the doublesex gene alters hearing in female Anopheles gambiae mosquitoes C_LIO_LIFemale mutant ears are anatomically and functionally distinct from both wild-type male and female; they show a substantial, but incomplete, masculinisation C_LIO_LIContrary to males, and similarly to females, the flagella of female mutants do not exhibit Self-Sustained Oscillations (SSOs) C_LIO_LITranscriptomic comparisons of ears uncovered molecular bases of auditory maleness, these were closely linked to molecular machinery of ciliary function C_LIO_LIComparisons with existing transcriptome from male testes revealed a substantial overlap between male ear and testicular ciliary motility machineries C_LI

neuroscience↗

bioRxiv2024

Adenosine signaling in glia modulates metabolic state-dependent behavior in Drosophila

An animals metabolic state strongly influences its behavior. Hungry animals prioritize food seeking and feeding behaviors, while sated animals suppress these behaviors to engage in other activities. Additionally, neuronal activity and synaptic transmission are among the most energy expensive processes. Yet neurons do not uptake nutrients from the circulation. Instead, glia fulfill this highly evolutionary conserved function. Recent studies have shown that glia can modulate neuronal activity and behavior. However, how different glia subtypes sense metabolic state and modulate neurons and behavior is incompletely understood. Here, we unravel two types of glia-mediated modulation of metabolic state-dependent behavior. In food-deprived flies, astrocyte-like and perineurial glia promote foraging and feeding, respectively, while cortex glia suppress these behaviors. We further show that adenosine and adenosine receptor modulate intracellular calcium levels in these glia subtypes, which ultimately controls behavior. This study reveals a new mechanism how different glia subtypes sense the metabolic state of the animal and modulate its behavior accordingly.

neuroscience↗

bioRxiv2017

SuperDCA for genome-wide epistasis analysis

The potential for genome-wide modeling of epistasis has recently surfaced given the possibility of sequencing densely sampled populations and the emerging families of statistical interaction models. Direct coupling analysis (DCA) has earlier been shown to yield valuable predictions for single protein structures, and has recently been extended to genome-wide analysis of bacteria, identifying novel interactions in the co-evolution between resistance, virulence and core genome elements. However, earlier computational DCA methods have not been scalable to enable model fitting simultaneously to 104-105 polymorphisms, representing the amount of core genomic variation observed in analyses of many bacterial species. Here we introduce a novel inference method (SuperDCA) which employs a new scoring principle, efficient parallelization, optimization and filtering on phylogenetic information to achieve scalability for up to 105 polymorphisms. Using two large population samples of Streptococcus pneumoniae, we demonstrate the ability of SuperDCA to make additional significant biological findings about this major human pathogen. We also show that our method can uncover signals of selection that are not detectable by genome-wide association analysis, even though our analysis does not require phenotypic measurements. SuperDCA thus holds considerable potential in building understanding about numerous organisms at a systems biological level.\n\nAuthor SummaryRecent work has demonstrated the emerging potential in statistical genome-wide modeling to uncover co-selection and epistatic interactions between polymorphisms in bacterial chromosomes from densely sampled population data. Here we develop the Potts model based approach further into a fully mature computational method which can be applied to most existing bacterial population genomic data sets in a straightforward manner. Our advances are relying on more efficient parameter scoring, highly optimized and parallelized open source C++ code, which does not rely on the computation-intensive polymorphism subsampling approximations used earlier. By analyzing the two largest available population samples of Streptococcus pneumoniae (the pneumococcus), we highlight several biological discoveries related to the survival of the pneumococcus and co-evolution of penicillin-binding loci, which were not uncovered by the earlier analyses. Our method holds considerable potential for building understanding about numerous organisms at a systems biological level.

genomics↗