Biology subjects

Tracey, W. D.

Publications and source records attributed to Tracey, W. D..

6 recordsLinked to original sources

bioRxiv2025

Genomics and reproductive biology of Leptopilina malgretoutensis Buffington, Lue, Davis & Tracey sp. nov. (Hymenoptera: Figitidae): An asexual parasitoid of Caribbean Drosophila

Drosophila and parasitic wasps in the genus Leptopilina have long been a model for understanding host-parasite interactions. Indeed, parasitic wasps are important drivers of ecological and evolutionary processes broadly, but we are generally lacking information about the diversity, natural history, and evolution of these relationships. We collected insects from the Caribbean Island of Saint Lucia, home to the eastern Caribbean dunni subgroup of Drosophila: a clade long appreciated for its recent patterns of speciation and adaptation. Here we present an integrative approach that incorporates natural history, taxonomy, physiology, and genomics to describe Leptopilina n. sp. Buffington, Lue, Davis & Tracey sp. nov. (Hymenoptera: Figitidae), a virulent parasitoid of dunni group flies, especially Drosophila antillea. Leptopilina n. sp. is nested within an early-branching clade of Leptopilina, offering insights into the evolution of this important genus of Drosophila parasitoids. We present a high-quality assembly for this wasps 1Gbp genome, and for its bacterial endosymbiont: Wolbachia strain "wLmal". Furthermore, we show that wLmal induces parthenogenesis in the wasp, and that these wasps are reliant upon their Wolbachia infections to produce female offspring. Finally, comparison to historical museum specimens indicate that Leptopilina n. sp. had been collected approximately 40 years prior from the nearby island of Guadeloupe and were also asexually reproducing. This work represents one of only a handful of studies in which field biology, taxonomy, systematics, genomics, and experimental biology are integrated into a species description: showcasing the possibilities for biodiversity research in the genomic era.

evolutionary biology↗

bioRxiv2024

Multiple mechanisms of action of an extremely painful venom

Evolutionary arms races between predator and prey can lead to extremely specific and effective defense mechanisms. Such defenses include venoms that deter predators by targeting nociceptive (pain-sensing) pathways. Through co-evolution, venom toxins can become extremely efficient modulators of their molecular targets. The venom of velvet ants (Hymenoptera: Mutillidae) is notoriously painful. The intensity of a velvet ant sting has been described as "Explosive and long lasting, you sound insane as you scream. Hot oil from the deep fryer spilling over your entire hand." [1] The effectiveness of the velvet ant sting as a deterrent against potential predators has been shown across vertebrate orders, including mammals, amphibians, reptiles, and birds [2-4]. The venoms low toxicity suggests it has a targeted effect on nociceptive sensory mechanisms [5]. This leads to the hypothesis that velvet ant venom targets a conserved nociception mechanism, which we sought to uncover using Drosophila melanogaster as a model system. Drosophila larvae have peripheral sensory neurons that sense potentially damaging (noxious) stimuli such as high temperature, harsh mechanical touch, and noxious chemicals [6-9]. These polymodal nociceptors are called class IV multidendritic dendritic arborizing (cIV da) neurons, and they share many features with vertebrate nociceptors, including conserved sensory receptor channels [10,11]. We found that velvet ant venom strongly activated Drosophila nociceptors through heteromeric Pickpocket/Balboa (Ppk/Bba) ion channels. Furthermore, we found a single venom peptide (Do6a) that activated larval nociceptors at nanomolar concentrations through Ppk/Bba. Drosophila Ppk/Bba is homologous to mammalian Acid Sensing Ion Channels (ASICs) [12]. However, the Do6a peptide did not produce behavioral signs of nociception in mice, which was instead triggered by other non-specific, less potent, peptides within the venom. This suggests that Do6a is an insect-specific venom component that potently activates insect nociceptors. Consistent with this, we showed that the velvet ants defensive sting produced aversive behavior in a predatory praying mantis. Together, our results indicate that velvet ant venom evolved to target nociceptive systems of both vertebrates and invertebrates, but through different molecular mechanisms.

neuroscience↗

bioRxiv2022

The motor pattern of rolling escape locomotion in Drosophila larvae

When undisturbed, Drosophila larvae move forward through their environment with sweeping waves of caudal to rostral muscle contraction [1, 2]. In stark contrast, nociceptive sensory stimuli (such as attacks by parasitoid wasps) trigger the larvae to roll across the substrate by corkscrewing around the long body axis [3, 4]. While studies have described the motor pattern of larval crawling [1, 2], the motor pattern of larval rolling escape locomotion remains unknown. Here, we have determined this pattern. To do so, we developed a high speed confocal time-lapse imaging preparation that allowed us to trigger rolling with optogenetics while simultaneously imaging a genetically encoded calcium sensor that was expressed in the muscles. Of the 30 muscles present in each larval abdominal hemisegment we find that only 11 muscles are consistently and specifically activated across segments during rolling. 8 additional muscles are more sparsely activated. Importantly, the sequential pattern of muscle recruitment during rolling is completely distinct from that of forward or reverse crawling. We discover that a roll involves a wave of muscle activation that propagates around the larval circumference (in the transverse plane of each segment) and involves four coactive muscle groups. A pattern of activation progresses from coactive ventral muscle groups to dorsal groups and then spreads across the midline to the contralateral dorsal muscle groups which then progresses back to the ventral groups. Finally, the direction of a roll (either clockwise or counterclockwise around the body) is determined by the clockwise or counterclockwise order of muscle group activation around the transverse plane.

neuroscience↗

bioRxiv2021

The Drosophila gene smoke alarm regulates nociceptor-epidermis interactions and thermal nociception behavior

The detection and processing of noxious sensory input depends on the proper growth and function of nociceptor sensory neurons in the peripheral nervous system. In Drosophila melanogaster, the class IV (cIV) multidendritic dendritic arborization (md-da) neurons detect noxious stimuli through their highly branched dendrites that innervate the epidermis of the larval body wall. Here, we describe requirements of a previously uncharacterized gene named smoke alarm (smal), a discoidin domain receptor, in cIV md-da dendrite morphogenesis and nociception behavior. We find that smal mutant larvae exhibit thermal hyperalgesia that is fully rescued with a BAC transgene containing smal. Consistent with this phenotype, a smal reporter gene was expressed in nociceptors and other peripheral sensory neurons. Smal::GFP protein localized to punctate structures throughout the cIV md-da neurons. We further show that smal loss-of-function results in reduced nociceptor dendrite branching. Interestingly, mammalian homologues of smal act as collagen receptors, and we find that smal mutant dendrites showed an increase in epidermal cell ensheathment relative to animals that are wild type for smal. Based on this phenotype we propose that Smal protein function is required for attachment of dendrites to the extracellular matrix (ECM) and the loss of this activity results in thermal hyperalgesia.

neuroscience↗

bioRxiv2019

Pseudouridine synthases in the RluA family negatively regulate Drosophila nociception.

Nociceptive neurons of Drosophila melanogaster larvae are characterized by highly branched dendritic processes whose proper morphogenesis relies on a large number of RNA-binding proteins. Post-transcriptional regulation of RNA in these dendrites has been found to play an important role in their function. Here, we investigate the neuronal functions of two putative RNA modification genes, RluA-1 and RluA-2, which are predicted to encode pseudouridine synthases. RluA-1 is specifically expressed in larval sensory neurons while RluA-2 expression is ubiquitous. Nociceptor-specific RNAi knockdown of RluA-1 caused hypersensitive nociception phenotypes, which were recapitulated with genetic null alleles. These were rescued with genomic duplication and nociceptor-specific expression of UAS-RluA-1-cDNA. As with RluA-1, RluA-2 loss of function mutants also displayed hyperalgesia. Interestingly, nociceptor neuron dendrites showed a hyperbranched morphology in the RluA-1 mutants. The latter may be a cause or a consequence of heightened sensitivity in mutant nociception behaviors. Author SummaryPseudouridine (Psi) is a C5-glycoside isomer of uridine and it is the most common posttranscriptional modification of RNAs, including noncoding tRNAs, rRNAs, snRNAs as well as mRNAs. Although first discovered in the 1950s, the biological functions of Psi in multicellular organisms are not well understood. Interestingly, a marker for sensory neurons in Drosophila encodes for a putative pseudouridine synthase called RluA-1. Here, we report our characterization of nociception phenotypes for larvae with RluA-1 loss of function along with that of a related gene RluA-2. Disrupting either or both RluA-1 and RluA-2 resulted in hypersensitive nociception. In addition, RluA-1 mutants have more highly branched nociceptor neurites that innervate the epidermis. Our studies suggest an important role for the RluA family in nociception. This may be through its action on RNAs that regulate neuronal excitability and/or dendrite morphogenesis.

genetics↗

bioRxiv2018

BMP Signaling Downstream of the Highwire E3 Ligase Sensitizes Nociceptors.

A comprehensive understanding of the molecular machinery important for nociception is essential to improving the treatment of pain. Here, we show that the BMP signaling pathway regulates nociception downstream of the E3 ubiquitin ligase highwire (hiw). Hiw loss of function in nociceptors caused antagonistic and pleiotropic phenotypes with simultaneous insensitivity to noxious heat but sensitized responses to optogenetic activation of nociceptors. Thus, hiw functions to both positively and negatively regulate nociceptors. We find that a sensory transduction-independent sensitization pathway was associated with BMP signaling. BMP signaling in nociceptors was up-regulated in hiw mutants, and nociceptor-specific expression of hiw rescued all nociception phenotypes including the increased BMP signaling. Blocking the transcriptional output of the BMP pathway with dominant negative Mad suppressed nociceptive hypersensitivity that was induced by interfering with hiw. The up-regulated BMP signaling phenotype in hiw genetic mutants could not be suppressed by mutation in wallenda suggesting that hiw regulates BMP in nociceptors via a wallenda independent pathway. In a newly established Ca2+ imaging preparation, we observed that up-regulated BMP signaling caused a significantly enhanced Ca2+ signal in the axon terminals of nociceptors that were stimulated by noxious heat. This response likely accounts for the nociceptive hypersensitivity induced by elevated BMP signaling in nociceptors. Finally, we showed that acute activation of BMP signaling in nociceptors was sufficient to sensitize nociceptive responses to optogenetically-triggered nociceptor activation without altering nociceptor morphology. Overall, this study demonstrates the previously unrevealed roles of the Hiw-BMP pathway in the regulation of nociception and provides the first direct evidence that up-regulated BMP signaling physiologically sensitizes responses of nociceptors and nociception behaviors.\n\nAuthor SummaryAlthough pain is a universally experienced sensation that has a significant impact on human lives and society, the molecular mechanisms of pain remain poorly understood. Elucidating these mechanisms is particularly important to gaining insight into the clinical development of currently incurable chronic pain diseases. Taking an advantage of the powerful genetic model organism Drosophila melanogaster (fruit flies), we unveil the Highwire-BMP signaling pathway as a novel molecular pathway that regulates the sensitivity of nociceptive sensory neurons. Highwire and the molecular components of the BMP signaling pathway are known to be widely conserved among animal phyla, from nematode worms to humans. Since abnormal sensitivity of nociceptive sensory neurons can play a critical role in the development of chronic pain conditions, a deeper understanding of the regulation of nociceptor sensitivity has the potential to advance effective therapeutic strategies to treat difficult pain conditions.

neuroscience↗