2025 · iScience
Using a female-specific isoform of doublesex to explore male-specific hearing in mosquitoes.
This publication investigates Using a female-specific isoform of doublesex to explore male-specific hearing in mosquitoes.

Generated from ORCID where available; fallback PubMed/NCBI records require manual review. Current Albert Lab members are underlined in the author lists.
2025 · iScience
This publication investigates Using a female-specific isoform of doublesex to explore male-specific hearing in mosquitoes.
2025 · iScience
This publication investigates The GABA(A) receptor RDL modulates the auditory sensitivity of malaria mosquitoes.
2025 · bioRxiv
Abstract Hearing begins when ears convert sound into neuronal excitation. The hearing organs of male Anopheles mosquitoes rank amongst the most sensitive ears evolved. Males use them to detect faint female flight tones within noisy mating swarms, but female flight tones largely lie above the male’s hearing range. We report a mechanism by which inaudible higher-frequency primary tones become audible through intrinsically generated, lower-frequency distortion tones. Distortion-evoked responses show ∼10-times greater sensitivity and 45% higher temporal precision than those of same-frequency primary tones. Moreover, self-sustained oscillations of the male’s ear dramatically reshape auditory frequency tuning and neuronal recruitment. By one mechanism, mosquito ears thus create audible signals and isolate these from the most salient frequencies of background noise. In audiology, distortions are used for diagnostics; their biological relevance, however, is unknown. Our results suggest that distortions are not mere by-products of the auditory process, but integral to its signaling logic.
2025 · Proceedings of the National Academy of Sciences
Distortion products are tones produced through nonlinear effects of a system simultaneously detecting two or more frequencies. These combination tones are ubiquitous to vertebrate auditory systems and are generally regarded as byproducts of nonlinear signal amplification. It has previously been shown that several species of infectious-disease-carrying mosquitoes utilize these distortion products for detecting and locating potential mates. Furthermore, the mechanical tuning curve of the male mosquito flagellum was shown not to be aligned with that of its sensory neural elements. Using a generic theoretical model for acoustic sensing, we evaluate the signal-detection advantages and disadvantages that are implied by these two schemes: distortion product detection and cascading a signal through multiple layers of oscillator elements of different characteristic frequency. Last, we show that the combination of these two schemes yields a signal detector with enhanced frequency selectivity and speed of response, thus enabling the detection of transient, narrowband flight tones.
2024 · bioRxiv
Malaria mosquitoes mate in crowded, and noisy, swarms. A vital stage of their precopulatory behaviour involves detecting the faint flight tone of a mating partner amidst the noise from hundreds of other mosquitoes. This exquisite sensory performance is enabled by a complex auditory system with remarkable features. One such feature is their vast efferent control system, which provides the mosquito ear with the required plasticity to adapt to various external and internal changes. In this paper, we study the auditory role of GABA, one of the main efferent signalling molecules in the mosquito ear, and its interactions with octopamine, another neurotransmitter of the efferent network. We show that GABA is released in the malaria mosquito auditory nerve and that GABA receptors are expressed in the ear, including the GABAA receptor Resistance to Dieldrin (RDL), a target for the evolution of insecticide resistance. Using picrotoxin to antagonize RDL receptors, we discovered multiple auditory effects of GABA at the mechanical and electrical level. At the mechanical level, blocking RDL promotes the erection of antennal fibrillae and the cessation of flagellar self-sustained oscillations. These effects are not observed in knockouts of the octopamine receptor AgOctbeta2, suggesting that RDL auditory mechanical effects are mediated through octopamine release in the mosquito ear. Electrically, picrotoxin injection increases the spontaneous firing of auditory neurons and direct current (DC) responses of the nerve to mechanical stimulation both in wildtype and AgOctbeta2 mutants, indicating that RDL may also modulate auditory sensitivity via octopamine-independent pathways. In summary, our experiments uncover distinct auditory roles of GABA, as well as synergistic roles with octopamine. The data show a fundamental role of RDL in controlling the auditory function of malaria mosquitoes and implicate RDL signalling in mating of natural malaria mosquito populations.
2024 · Hearing Research
This publication investigates A burden shared: The evolutionary case for studying human deafness in Drosophila.
2023 · bioRxiv
Despite the artificial conditions, flight tone recordings taken from tethered mosquitoes can provide valuable information on the acoustic signals produced by male and female mosquitoes. Although auditory responsiveness appears to be largely (and possibly exclusively) restricted to males, the flight tones of both sexes have sensory-ecological relevance, as it is the mixing of the two tones that produces audibility in males and thereby facilitates reproduction. This protocol describes how to record wing flapping from mounted mosquitoes and how to estimate wingbeat frequencies from those recordings.
2023 · bioRxiv
Phonotaxis experiments can provide information on the spectrum of sounds relevant to mosquito acoustic behaviors. It is widely known that males of disease-transmitting species are attracted to tones with frequencies resembling the wingbeat frequencies of their conspecific females. Thus, phonotaxis experiments can be coupled with wingbeat frequency measurements to inform the development of vector control tools such as acoustic traps and lures. This protocol describes how to set up and execute a phonotaxis experiment.
2023 · bioRxiv
Immunohistochemistry has played a major role in improving our understanding of the anatomy and function of the nervous system. The use of fluorescent dyes that label different antigens reveals how biological tissues are built and how interactions between cells take place. Obtaining this information is particularly important in the case of the mosquito ear given its highly complex anatomy. This protocol describes an immunohistochemical technique to stain the mosquito ear. The first steps of the procedure include the embedding of the tissue in albumin-gelatin and its sectioning into thin slices to allow antibody penetration. The immunohistochemical procedure can be exploited to detect protein expression and localization by using antibodies specifically raised against the protein of interest or that recognize epitope tags fused to proteins using genome editing methods.
2023 · Nature Communications
Abstract Malaria mosquitoes acoustically detect their mating partners within large swarms that form transiently at dusk. Indeed, male malaria mosquitoes preferably respond to female flight tones during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing in the species Anopheles gambiae . Among them, octopamine stands out as an auditory modulator during swarm time. In-depth analysis of octopamine auditory function shows that it affects the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and controls the erection of antennal fibrillae. We show that two α- and β-adrenergic-like octopamine receptors drive octopamine’s auditory roles and demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings highlight octopamine as key for mosquito hearing and mating partner detection and as a potential novel target for mosquito control.
2023 · bioRxiv
Electrophysiological recordings taken from the antennal nerve can provide essential information on the general auditory condition of the mosquito tested. Furthermore, electrophysiological recordings provide detailed information on what types of stimulation induce the largest nerve responses. When these are used in conjunction with a vibrometer to measure the corresponding movement of the antennal ear during stimulation, a comprehensive overview of hearing function can be obtained. This protocol can be applied to male and female adults from any mosquito strain and can be scaled relative to available resources.
2023 · bioRxiv
The acoustic physiology of mosquitoes is perhaps the most complex within the entire insect class. Past research has uncovered several of its—sometimes stunningly unconventional—principles, but many mysteries remain. Their solution necessitates a concerted transdisciplinary effort to successfully link the neuroanatomical and biophysical properties of mosquito flagellar ears to the behavioral ecology of entire mosquito populations. Neuroanatomically, mosquito ears can rival those of humans in both complexity and sheer size. The approximately 16,000 auditory hair cells within the human organ of Corti, for example, are matched by the approximately 16,000 auditory neurons in the Johnston's organ of a male Anopheles mosquito. Both human and mosquito ears receive very extensive efferent innervation, which modulates their function in ways that are as yet poorly understood. Different populations of neuronal and nonneuronal cell types divide the labor of the mosquito ear amongst themselves. Yet, what exactly this labor is, and how it is achieved, is at best vaguely known. For the majority of mosquitoes, biologically relevant sounds are inextricably linked to their flight tones. Either these flight tones are (directly) the sounds of interest or they contribute (indirectly) to the production of audible sound through a process called nonlinear distortion. Finally, male ears can generate tones themselves: The generation of an internal “phantom copy” of a female flight tone (or self-sustained oscillation ) is believed to aid the male hearing process. Here, we introduce protocols that target the mosquitoes’ auditory neuroanatomy, electrophysiology, and behavior to help shed light on some of these issues.
2022 · Science Advances
By beating their wings faster around sunset, male Anopheles mosquitoes sensitize their auditory system to female flight tones.
2022 · bioRxiv
Hearing is an essential sense in the life cycle of malaria mosquitoes. Within large swarms formed transiently at dusk, mosquitoes acoustically recognize their mating partners by their wingbeats. Indeed, malaria mosquitoes only respond to the flight tones of mating partners during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are still largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing. Among them, octopamine stands out as regulator of the auditory performance during swarm time. To explore octopamine roles in mosquito hearing, we carried out an in-depth analysis of octopamine-mediated effects on auditory function. We found that octopamine affects the properties of the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and it controls the erection of antennal fibrillae in males. We found that two different receptors are driving octopamine auditory roles, including a novel beta octopamine receptor. We also demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings identify octopamine signalling as a key component of hearing and mating partner detection in malaria mosquitoes, and as a potential novel target for mosquito control.
2022 · Frontiers in Cell and Developmental Biology
Meniere’s disease (MD) is an inner ear disorder characterised by recurrent vertigo attacks associated with sensorineural hearing loss and tinnitus. Evidence from epidemiology and Whole Exome Sequencing (WES) suggests a genetic susceptibility involving multiple genes, including α-Dystrobrevin ( DTNA ). Here we investigate a Drosophila model. We show that mutation, or knockdown, of the DTNA orthologue in Drosophila , Dystrobrevin ( Dyb ), results in defective proprioception and impaired function of Johnston’s Organ (JO), the fly’s equivalent of the inner ear. Dyb and another component of the dystrophin-glycoprotein complex (DGC), Dystrophin ( Dys ), are expressed in support cells within JO. Their specific locations suggest that they form part of support cell contacts, thereby helping to maintain the integrity of the hemolymph-neuron diffusion barrier, which is equivalent to a blood-brain barrier. These results have important implications for the human condition, and notably, we note that DTNA is expressed in equivalent cells of the mammalian inner ear.
2021 · iScience
This publication investigates Turnover and activity-dependent transcriptional control of NompC in the Drosophila ear.
2021 · bioRxiv
Abstract Mating swarms of malaria mosquitoes form every day at sunset throughout the tropical world, they typically last less than 30 minutes. Activity patterns must thus be highly synchronized between the sexes. Moreover, males must be able to identify the few sporadically entering females by detecting the females’ faint flight tones. We here show that the Anopheles circadian clock ensures a tight synchrony of male and female activity and –importantly – also retunes the males’ acoustic detection system: by lifting their own flight tones at dusk, males actively enhance the audibility of females. The reported phenomenon of ‘harmonic convergence’ is a random by-product of the mosquitoes’ flight tone variance. Intriguingly, flight tones of individual mosquitoes occupy narrow –partly non-overlapping-frequency ranges, suggesting that the audibility of individual females varies across males. One Sentence Summary Male mosquitoes sharpen their hearing at sunset.
2020 · Scientific Reports
Abstract Age-related hearing loss (ARHL) is a threat to future human wellbeing. Multiple factors contributing to the terminal auditory decline have been identified; but a unified understanding of ARHL - or the homeostatic maintenance of hearing before its breakdown - is missing. We here present an in-depth analysis of homeostasis and ageing in the antennal ears of the fruit fly Drosophila melanogaster . We show that Drosophila , just like humans, display ARHL. By focusing on the phase of dynamic stability prior to the eventual hearing loss we discovered a set of evolutionarily conserved homeostasis genes. The transcription factors Onecut (closest human orthologues: ONECUT2, ONECUT3), Optix (SIX3, SIX6), Worniu (SNAI2) and Amos (ATOH1, ATOH7, ATOH8, NEUROD1) emerged as key regulators, acting upstream of core components of the fly’s molecular machinery for auditory transduction and amplification. Adult-specific manipulation of homeostatic regulators in the fly’s auditory neurons accelerated - or protected against - ARHL.
2020 · Current Opinion in Insect Science
This publication investigates Buzzkill: targeting the mosquito auditory system.
2020 · bioRxiv
Abstract Background The release of genetically modified mosquitoes which use gene-drive mechanisms to suppress reproduction in natural populations of Anopheles mosquitoes is one of the scientifically most promising methods for malaria transmission control. However, many scientific, regulatory and ethical questions remain before transgenic mosquitoes can be utilised in the field. Mutations which reduce an individual’s reproductive success are likely to create strong selective pressures to evolve resistance. It is thus crucial that the targeted population collapses as rapidly and as completely as possible to reduce the available time for the emergence of drive-resistant mutations. At a behavioural level, this means that the gene-drive carrying mutants should be at least as (and ideally more) sexually attractive than the wildtype population they compete against. A key element in the copulatory negotiations of Anopheles mosquitoes is their acoustic courtship. We therefore analysed sound emissions and acoustic preference in a doublesex mutant previously used to successfully collapse caged colonies of Anopheles gambiae s . l .. Methods The flight tones produced by the beating of their wings form the signals for acoustic mating communication in Anopheles species. We assessed the acoustic impact of the disruption of a female-specific isoform of the doublesex gene ( dsxF ) on the wing beat frequency (WBF; measured as flight tone ) of both males (XY) and females (XX) in homozygous dsxF - mutants ( dsxF -/- ), heterozygous dsxF - carriers ( dsxF +/- ) and G3 ‘wildtype’ dsxF + controls ( dsxF +/+ ). To exclude non-genetic influences, we controlled for temperature and measured wing lengths for all experimental animals. We used a phonotaxis assay to test the acoustic preferences of mutant and control mosquitoes. Results A previous study demonstrated an altered phenotype only for females homozygous for the disrupted dsx allele ( dsxF -/- ), who appear intersex. No phenotypic changes were observed for heterozygous carriers or males, suggesting that the female-specific dsxF allele is haplosufficient. We here identify significant, dose-dependent increases in the flight tones of both dsxF -/- and dsxF +/- females when compared to dsxF +/+ control females. Flight tone frequencies in all three female genotypes remained significantly lower than in males, however. When tested experimentally, males showed stronger phonotactic responses to the flight tones of control dsxF +/+ females. While flight tones from dsxF +/- and dsxF -/- females also elicited positive phonotactic behaviour in males, this was significantly reduced compared to responses to control tones. We found no evidence of phonotactic behaviour in any female genotype tested. None of the male genotypes displayed any deviations from the control condition. Conclusions A key prerequisite for copulation in anopheline mosquitoes is the phonotactic attraction of males towards female flight tones within large - spatially and acoustically crowded - mating swarms. Reductions in acoustic attractiveness of released mutant lines, as reported here for heterozygous dsxF +/- females, reduce the line’s mating efficiency, and could consequently reduce the efficacy of the associated population control effort. Assessments of caged populations may not successfully reproduce the challenges posed by natural mating scenarios. We propose to amend existing testing protocols in order to more faithfully reflect the competitive conditions between a mutant line and the wildtype population it is meant to interact with. This should also include novel tests of ‘acoustic fitness’. In line with previous studies, our findings confirm that disruption of the female-specific isoform dsxF has no effect on males; for some phenotypic traits, such as female flight tones, however, the effects of dsxF appear to be dose-dependent rather than haplosufficient.
2020 · Parasites & Vectors
Abstract Background Release of gene-drive mutants to suppress Anopheles mosquito reproduction is a promising method of malaria control. However, many scientific, regulatory and ethical questions remain before transgenic mosquitoes can be utilised in the field. At a behavioural level, gene-drive carrying mutants should be at least as sexually attractive as the wildtype populations they compete against, with a key element of Anopheles copulation being acoustic courtship. We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae ( s.l. ) cages. Methods Anopheles rely on flight tones produced by the beating of their wings for acoustic mating communication. We assessed the impact of disrupting a female-specific isoform of the doublesex gene ( dsxF ) on the wing beat frequency (WBF; measured as flight tone ) of males (XY) and females (XX) in homozygous dsxF − mutants ( dsxF −/− ), heterozygous dsxF − carriers ( dsxF +/− ) and G3 dsxF + controls ( dsxF + / + ). To exclude non-genetic influences, we controlled for temperature and wing length. We used a phonotaxis assay to test the acoustic preferences of mutant and control mosquitoes. Results A previous study showed an altered phenotype only for dsxF −/− females, who appear intersex, suggesting that the female-specific dsxF allele is haplosufficient. We identified significant, dose-dependent increases in the WBF of both dsxF −/− and dsxF +/− females compared to dsxF + / + females. All female WBFs remained significantly lower than male equivalents, though. Males showed stronger phonotactic responses to the WBFs of control dsxF + / + females than to those of dsxF +/− and dsxF −/− females. We found no evidence of phonotaxis in any female genotype. No male genotypes displayed any deviations from controls. Conclusions A prerequisite for anopheline copulation is the phonotactic attraction of males towards female flight tones within mating swarms. Reductions in mutant acoustic attractiveness diminish their mating efficiency and thus the efficacy of population control efforts. Caged population assessments may not successfully reproduce natural mating scenarios. We propose to amend existing testing protocols to better reflect competition between mutants and target populations. Our findings confirm that dsxF disruption has no effect on males; for some phenotypic traits, such as female WBFs, the effects of dsxF appear dose-dependent rather than haplosufficient.
2018 · Nature Communications
Abstract Hearing is essential for the courtship of one of the major carriers of human disease, the mosquito. Males locate females through flight-tone recognition and both sexes engage in mid-air acoustic communications, which can take place within swarms containing thousands of individuals. Despite the importance of hearing for mosquitoes, its mechanisms are still largely unclear. We here report a multilevel analysis of auditory function across three disease-transmitting mosquitoes ( Aedes aegypti , Anopheles gambiae and Culex quinquefasciatus ). All ears tested display transduction-dependent power gain. Quantitative analyses of mechanotransducer function reveal sex-specific and species-specific variations, including male-specific, highly sensitive transducer populations. Systemic blocks of neurotransmission result in large-amplitude oscillations only in male flagellar receivers, indicating sexually dimorphic auditory gain control mechanisms. Our findings identify modifications of auditory function as a key feature in mosquito evolution. We propose that intra-swarm communication has been a driving force behind the observed sex-specific and species-specific diversity.
2018 · Frontiers in Behavioral Neuroscience
This publication investigates How Many Clocks, How Many Times? On the Sensory Basis and Computational Challenges of Circadian Systems.
2017 · Journal of Biological Rhythms
In Drosophila, as in other animals, the circadian clock is a singular entity in name and concept only. In reality, clock functions emerge from multiple processes and anatomical substrates. One distinction has conventionally been made between a central clock (in the brain) and peripheral clocks (e.g., in the gut and the eyes). Both types of clock generate robust circadian oscillations, which do not require external input. Furthermore, the phases of these oscillations remain exquisitely sensitive to specific environmental cues, such as the daily changes of light and temperature. When these cues conflict with one another, the central clock displays complex forms of sensory integration; how peripheral clocks respond to conflicting input is unclear. We therefore explored the effects of light and temperature misalignments on peripheral clocks. We show that under conflict, peripheral clocks preferentially synchronize to the light stimulus. This photic dominance requires the presence of the circadian photoreceptor, Cryptochrome.
2017 · eLife
Animals are characterized by a set of highly conserved developmental regulators. Changes in the cis-regulatory elements of these regulators are thought to constitute the major driver of morphological evolution. However, the role of coding sequence evolution remains unresolved. To address this question, we used the Atonal family of proneural transcription factors as a model. Drosophila atonal coding sequence was endogenously replaced with that of atonal homologues (ATHs) at key phylogenetic positions, non-ATH proneural genes, and the closest homologue to ancestral proneural genes. ATHs and the ancestral-like coding sequences rescued sensory organ fate in atonal mutants, in contrast to non-ATHs. Surprisingly, different ATH factors displayed different levels of proneural activity as reflected by the number and functionality of sense organs. This proneural potency gradient correlated directly with ATH protein stability, including in response to Notch signaling, independently of mRNA levels or codon usage. This establishes a distinct and ancient function for ATHs and demonstrates that coding sequence evolution can underlie quantitative variation in sensory development and function.
2016 · Cell Reports
This publication investigates Sensory Conflict Disrupts Activity of the Drosophila Circadian Network.
2016 · Current Biology
This publication investigates Comparative Aspects of Hearing in Vertebrates and Insects with Antennal Ears.
2015 · Journal of Comparative Physiology A
This publication investigates Prestin is an anion transporter dispensable for mechanical feedback amplification in Drosophila hearing.
2015 · Current Opinion in Neurobiology
This publication investigates Hearing in Drosophila.
2014 · Science
Coordinating the Clock In flies, the mechanosensory chordotonal organs help to coordinate the effects of temperature on circadian cycles. Simoni et al. (p. 525 ) provide a mechanism by which mechanosensory input is processed to help to synchronize the biological clock in Drosophila melanogaster . The chordotonal organs, which have similarities to the mammalian ear, were also required for sensation of a vibration stimulus and its effects on the endogenous brain clock. The chordotonal organs, present in the joints of the limbs, provide neuronal signals that allow the animal to sense its position or posture—and thus might mediate feedback of a range of behaviors onto the endogenous biological clock.
2010 · European Journal of Neuroscience
Abstract Vertebrate inner‐ear hair cells use mechanical feedback to amplify sound‐induced vibrations. The gain of this ‘cochlear amplifier’ is centrally controlled via efferent fibres that, making synaptic contacts with the hair cells, modulate the feedback gain. The sensory neurons of the Drosophila ear likewise employ mechanical feedback to assist sound‐evoked vibrations, yet whether this neuron‐based feedback is also subject to efferent control has remained uncertain. We show here that the function of Drosophila auditory neurons is independent of efferent modulation, and that no synaptic transmission is needed to control the gain of mechanical feedback amplification. Immunohistochemical, mechanical and electrophysiological analyses revealed that the Drosophila auditory organ lacks peripheral synapses and efferent innervations, and that blocking synaptic transmission in a pan‐neural manner does not affect the afferent electrical activity of the sensory neurons or the mechanical feedback gain. Hence, unlike the cochlear amplifier of vertebrates, mechanical feedback amplification in Drosophila is not associated with an efferent control system but seems to be a purely local process that is solely controlled peripherally within the ear itself.
2010 · Nature Communications
This publication investigates A doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia.
2009 · Neuron
This publication investigates Temperature entrainment of Drosophila's circadian clock involves the gene nocte and signaling from peripheral sensory tissues to the brain.
2007 · Current Biology
This publication investigates Mechanical signatures of transducer gating in the Drosophila ear.
2007 · Fly
This publication investigates Drosophila mechanotransduction--linking proteins and functions.
2005 · Proceedings of the National Academy of Sciences
In insects and vertebrates alike, hearing is assisted by the motility of mechanosensory cells. Much like pushing a swing augments its swing, this cellular motility is thought to actively augment vibrations inside the ear, thus amplifying the ear's mechanical input. Power gain is the hallmark of such active amplification, yet whether and how much energy motile mechanosensory cells contribute within intact auditory systems has remained uncertain. Here, we assess the mechanical energy provided by motile mechanosensory neurons in the antennal hearing organs of Drosophila melanogaster by analyzing the fluctuations of the sound receiver to which these neurons connect. By using dead WT flies and live mutants ( tilB 2 , btv 5P1 , and nompA 2 ) with defective neurons as a background, we show that the intact, motile neurons do exhibit power gain. In WT flies, the neurons lift the receiver's mean total energy by 19 zJ, which corresponds to 4.6 times the energy of the receiver's Brownian motion. Larger energy contributions (200 zJ) associate with self-sustained oscillations, suggesting that the neurons adjust their energy expenditure to optimize the receiver's sensitivity to sound. We conclude that motile mechanosensory cells provide active amplification; in Drosophila , mechanical energy contributed by these cells boosts the vibrations that enter the ear.