Biology subjects

Wu, S.-F.

Publications and source records attributed to Wu, S.-F..

8 recordsLinked to original sources

bioRxiv2026

A Conserved SIFamide Circuit Functions as the Insect Vagus Nerve

The insect functional homolog of the mammalian vagus nerve has remained elusive. Here, we identify the SIFamide (SIFa) peptidergic circuit as this homolog in Drosophila melanogaster. SIFa neurons project the longest axons from the brain to the hindgut ampulla, forming synapses with peripheral SIFa-receptor (SIFaR) neurons originating in the abdominal ganglion. This circuit is functionally plastic: sexual experience enhances synaptic strength at the hindgut, increasing excretion while reducing mating duration to to favor energy conservation and metabolic recovery. Mechanistically, this shift involves octopaminergic/tyraminergic gating and SIFa-mediated modulation of Adipokinetic Hormone (AKH) from the corpora cardiaca. We further uncover a feedback loop in which SIFaR/Allatostatin-A (AstA) neurons project back to the brain, signaling hindgut physiological status to SIFa neurons via AstA-R1. This hindgut projection is conserved across diverse insect orders. Thus, the SIFa-SIFaR circuit constitutes an evolutionarily conserved "insect vagus nerve" that integrates metabolic state and reproductive history to optimize survival strategies.

neuroscience↗

bioRxiv2026

A pesticide hijacks a neurohormonal circuit to block ovulation in insects

The global decline of insect populations threatens ecosystem stability, yet the hidden physiological impacts of sublethal pesticide exposure remain largely uncharted. Here we show that emamectin benzoate (EB), a widely used insecticide, suppresses female fertility not by disrupting egg development, but by specifically blocking ovulation. Through a systematic genetic screen in Drosophila, we identify the glutamate-gated chloride channel GluCl in a discrete set of octopaminergic neurons as the primary neural target. EB subverts the activity of this circuit, thereby impairing octopamine-dependent follicle rupture, suppressing ovarian ecdysteroid signaling, and altering oviduct muscle dynamics--three coordinated processes essential for egg release. Strikingly, this ovulatory blockade is recapitulated in diverse dipteran pests and disease-vector mosquitoes, revealing a conserved vulnerability. Our findings establish a neurohormonal mechanism by which a common agrochemical hijacks reproductive control, and they expose ovulation as a critical, hitherto unrecognized nexus between environmental chemicals and insect population dynamics. SignificanceSublethal pesticide exposure can profoundly alter insect physiology beyond acute toxicity, yet the underlying mechanisms remain unclear. Here, we show that emamectin benzoate (EB), a widely used avermectin insecticide, suppresses ovulation and female fecundity in Drosophila by disrupting octopaminergic signaling, follicle rupture, and oviduct muscle contraction. Mechanistically, EB acts through GluCl-dependent neural pathways to impair ovulation-related processes and reproductive muscle dynamics. Notably, these inhibitory effects are conserved across multiple dipteran species, suggesting that reproductive suppression represents a broader physiological consequence of EB exposure. Our findings reveal a previously unrecognized neuro-reproductive mechanism of pesticide action and provide new insight into how sublethal insecticide exposure may influence insect population dynamics.

neuroscience↗

bioRxiv2025

Internal mechanosensory feedback modulates central pattern generation to coordinate ovulation in Drosophila

Ovulation is a prerequisite for successful reproduction and requires precise coordination of muscle contractions, especially to propel eggs from the paired lateral oviducts into the common oviduct. Although internal mechanosensation is expected to provide critical feedback for this process, the sensorimotor circuitry and mechanisms by which sensory feedback shapes motoneuron activity and coordinates oviduct contractions are still poorly known. Here, in Drosophila, we identify a novel pair of multidendritic mechanosensory neurons (mdn-LO) in the lateral oviducts that express the mechanosensitive channels TMC (transmembrane channel-like protein), PPK (pickpocket), and Piezo. We show that TMC is essential for coordinated ovulation; tmc mutation or neuron-specific knockdown increases egg-jamming at the junction between the lateral and the common oviduct. In contrast, ppk or Piezo mutants display reduced egg-laying but no jamming. Calcium imaging reveals that the mdn-LO neurons are rhythmically activated by oviduct contractions, and chemogenetic stimulation of these neurons triggers muscle contractions. Genetic manipulations of the mdn-LO neurons disrupt egg passage and induce egg-jamming. The axons of the mdn-LO neurons form functional contacts with female-specific oviduct motoneurons in the abdominal neuromeres that express insulin-like peptide 7 (ILP7) and glutamate. Activation of mdn-LO neurons triggers Ca{superscript 2} activity in ILP7 motoneurons and elicits rhythmic oviduct contractions. Importantly, the ILP7 motoneurons exhibit spontaneous rhythmic Ca{superscript 2} activity that is modulated by oviduct contractions and egg movement. Furthermore, triggering activity in the ILP7 neurons induces egg-jamming. Finally, knockdown of ILP7 peptide affects the rate of ovulation, but plays no role in egg jamming, which instead is likely induced by colocalized glutamate. In summary, our study identifies a novel circuit, including the TMC-expressing mdn-LO neurons and a small set of ILP7 motoneurons, that organizes an innate behavior by coupling strategic sensory information and rhythmical motor output to ensure bilateral coordination of oviduct contractions to prevent egg jamming during oviposition. SignificanceOvulation requires precisely coordinated contractions of the lateral oviducts to propel eggs into the common oviduct without jamming. Yet the sensory cells and mechanotransduction channels that coordinate movement through the paired lateral oviducts remain unclear. Here, we identify a novel pair of lateral-oviduct multidendritic neurons (mdn-LO) that express the conserved mechanosensory channels TMC (transmembrane channel-like protein), PPK (pickpocket), and Piezo, and show that TMC is uniquely required to prevent egg jamming at the junction between the lateral and common oviducts. The mdn-LO neurons are activated by oviduct contractions and relay signals to female-specific glutamatergic motoneurons in the abdominal neuromere. These paired oviduct motoneurons are rhythmically active and regulate contractions of the lateral oviducts. Together, our findings demonstrate that TMC-mediated mechanosensory feedback fine-tunes motor output to ensure coordinated ovulation and successful reproduction.

neuroscience↗

bioRxiv2025

Endogenous corazonin signaling modulates the post-mating switch in behavior and physiology in females of the brown planthopper and Drosophila

Mating in insects typically triggers a post-mating response (PMR) in females, characterized by reduced receptivity to re-mating and increased oviposition, which ensures numerous and viable offspring and male paternity. This PMR is induced by male seminal factors, such as sex peptide in Drosophila melanogaster, as well as intrinsic female signaling components. The latter signaling remains poorly understood in most insects, including the devastating rice pest, the brown planthopper (BPH) Nilaparvata lugens. Here, we show that the neuropeptide corazonin (CRZ) and its receptor (CrzR) are critical for the PMR in female BPHs. Peptide injection, RNAi knockdown, and CRISPR/Cas9 mutagenesis confirm that intact CRZ signaling reduces re-mating frequency and increases ovulation in mated BPH females. The CrzR is highly expressed in the female reproductive tract, and CrzR knockdown phenocopies CRZ diminishment. Importantly, female CRZ/CrzR signaling is required for male seminal factors, such as the peptide maccessin, to induce the PMR; with disrupted CrzR signaling, injection of seminal fluid or maccessin fails to reduce female receptivity. Notably, CRZ is not produced in male accessory glands (MAGs) of BPHs and thus not transferred during copulation. We furthermore demonstrate that also in D. melanogaster disrupted CRZ signaling increases female re-mating and reduces oviposition, while CRZ injection suppresses virgin receptivity and increases oviposition. Finally, we detected no CRZ in the MAG of D. melanogaster, supporting its role as an endogenous signal in the female PMR also in this species. In summary, our findings reveal a conserved role of endogenous CRZ signaling in regulating the female PMR and demonstrate that female CRZ signaling and male-derived signals cooperate to induce post-mating transitions in BPHs and D. melanogaster. CRZ is a paralog of the peptide gonadotropin-releasing hormone, known to regulate reproduction in vertebrates, including humans, suggesting evolutionary conservation of an ancient function.

genetics↗

bioRxiv2024

A novel male accessory gland peptide reduces female post-mating receptivity in the brown planthopper

Mating in insects commonly induces a profound change in the physiology and behavior of the female that serves to secure numerous and viable offspring and to ensure paternity for the male by reducing receptivity of the female to further mating attempts. Here, we set out to characterize the post-mating response (PMR) in a pest insect, the brown planthopper (BPH) Nilaparvata lugens and to identify a functional analog of sex peptide (SP) and/or other seminal fluid factors that contribute to the PMR in Drosophila. We find that BPHs display a distinct PMR that lasts for about 4 days and includes a change in female behavior with decreased receptivity to males and increased oviposition. Extract from male accessory glands (MAG) injected into virgin females triggers a similar PMR, lasting about 24h. Since SP does not exist in BPHs, we screened for candidate mediators by performing a transcriptional and proteomics analysis of MAG extract. We identified a novel 51 amino acid peptide present only in the MAG and not in female BPHs. This peptide, that we designate maccessin (macc), affects the female PMR. Females mated by males with macc knockdown display receptivity to wild type males in a second mating, which does not occur in controls. However, oviposition is not affected. Injection of recombinant macc reduces female receptivity, with no effect on oviposition. Thus, macc is so far the only candidate seminal fluid peptide that promotes a PMR in BPHs. Our analysis suggests that the gene encoding the macc precursor is restricted to species closely related to BPHs. Author summaryIn insects, mating often induces a long-lasting change in the female behavior and physiology, called a post-mating response (PMR). This ensures numerous and viable offspring, but also serves to secure paternity for the male by inhibiting the female receptivity to further mating attempts. Here, we demonstrate that a pest insect, the brown planthopper (BPH) Nilaparvata lugens, also displays a PMR with decreased receptivity to further mating and increased egg laying. We furthermore find that seminal fluid extracted from the male accessory gland of BPHs injected into females generates a PMR. Next, we identified a novel peptide unique to the male accessory gland (designated maccessin) and demonstrate that this peptide is responsible for the reduced receptivity in the PMR, but does not affect egg laying. The gene encoding maccessin appears unique to close relatives of N. lugens. This is similar to a Drosophila male accessory gland factor, sex peptide, which is known to induce a PMR, and occurs only in a limited number of Drosophila species.

neuroscience↗

bioRxiv2024

First-male sperm precedence in polyandrous Spodoptera frugiperda allows sterile males induce population suppression

Males respond to intense sperm competition by adapting reproductive strategies to promote fertilization success, which is critical for population reproduction. Thus, investigating the patterns and mechanisms of sperm competition is crucial for the development and application of pest population management techniques. In this study, we analyzed the sperm precedence pattern of a major pest, the fall armyworm, and used this pattern to manage the pest population. First, we found that females had a post-mating response and did not gain direct benefit through multiple mating. Next, in a double mating experiment, we used a molecular marker created by CRISPR/Cas9 to determine that most females use only the sperm of the first male to produce offspring. To further explore the role of fertilizing sperm in sperm competition, we constructed a sterile male line with eupyrene sperm defect by knocking out the B2t gene. Interestingly, two round mating assays showed that first mating with B2t-null males inhibited sperm fertilization from a second wild-type male. In other words, prior mating with B2t-null males significantly reduced the fertility and fecundity of females. Based on this finding, we continued to explore whether sperm-deficient sterile males could be used in the management of FAW populations. Cage experiments and mathematical modeling analyses showed that the release of excess B2t-null males induced population suppression. Our study expands our knowledge of sperm competition patterns in lepidopteran. In addition, our study provides a paradigm to develop and apply genetic control methods based on sperm competition outcome in polyandrous pests. SignificanceSperm competition is essential for maintaining population reproduction. Understanding patterns and mechanisms of sperm competition facilitates the development of appropriate pest genetic control methods. Here, we describe that a globally major pest, the fall armyworm displays the first-male sperm precedence pattern. Interestingly, first mating with B2t-null males, which produces non-functional eupyrene sperm, significantly reduces the fertility and fecundity of females. That means that the ejaculate of the first male, even if its eupyrene sperm are defective, can inhibit sperm fertilization from a second wild-type male. Based on this, the release of excess B2t-null males significantly suppresses FAW populations. These results suggest that future development of genetic control techniques based on targeting nucleated sperm can effectively control FAW populations.

zoology↗

bioRxiv2023

Pesticide-induced resurgence of the brown planthopper is mediated by diverse actors that promote juvenile hormone biosynthesis and female fecundity

Pesticide-induced resurgence, increases in pest insect populations following pesticide application, is a serious threat to the sustainable control of many highly damaging crop pests. Resurgence can result from pesticide-enhanced pest reproduction, however, the molecular mechanisms mediating this process remain unresolved. Here we show that brown planthopper (BPH) resurgence in rice crops following exposure to sublethal doses of the pesticide emamectin benzoate (EB) results from the coordinated action of a suite of genes that regulate juvenile hormone (JH) levels, resulting in increased JH titer in adult females and enhanced fecundity. We demonstrate that EB treatment at sublethal levels results in profound changes in female BPH fitness including increased egg maturation and oviposition. This enhanced reproductive fitness results from the EB-mediated upregulation of key genes involved in the regulation of JH, including JHAMT and Kr-h1 and the downregulation of allatostatin (AstA) and allatostatin receptor (AstAR) expression. AstA signaling is known to inhibit the production of JH in the corpora allata and hence EB exposure diminishes this inhibitory action. We find that the changes in gene expression following EB exposure are caused by the allosteric action of this insecticide on its molecular target, the glutamate-gated chloride channel (GluCl). Collectively, these results provide mechanistic insights into the regulation of negative pesticide-induced responses in insects and reveal some key actors involved in the JH-signaling pathway that underpin pesticide resurgence. SignificancePesticides remain a key means of controlling many of the worlds insect pests. However, in some cases, pesticide applications can result in resurgence of pest populations due to pesticide-induced increases in fecundity. In the current study, we show that pesticide resurgence in the brown planthopper (BPH) following exposure to the insecticide emamectin benzoate (EB) results from the transcriptional reprogramming of a diverse suite of positive and negative regulators of juvenile hormone (JH), a critical regulator of insect development and reproduction. This in turn leads to profound increases in female BPH reproductive fitness and enhanced fecundity. Our findings unravel some of the molecular mechanisms mediating pesticide-induced pest resurgence and inform the development of novel strategies to control highly damaging crop pests.

ecology↗

bioRxiv2020

Cholecystokinin-like Peptide Mediates Satiety by Inhibiting Sugar Attraction

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. This Gr64f regulation is by direct action of SK neurons on Gr64f-expressing neurons of the proboscis and proleg tarsi that co-express the SK receptor CCKLR-17D3. Our findings thus demonstrate how nutritional state induces peptide signaling to modulate sweet perception and thereby feeding behavior.

neuroscience↗