Publications

This work looks at how fruit flies build the precise wiring of their sense of smell during development. Odor-detecting neurons in the fly's antenna need to connect to exactly the right partner neurons deeper in the brain, out of about 60 possible matches, and scientists have long wondered what molecular "name tags" let each neuron find its correct partner.

We focused on two families of proteins, called Beats and Sides, that sit on the surface of neurons and can stick to each other. By engineering flies so that each of these genes lights up green wherever it's turned on, we mapped out which olfactory neurons and their partner neurons use which Beat and Side proteins, discovering that every neuron type uses its own distinctive combination, almost like a barcode. Surprisingly, when they experimentally disrupted one specific matching pair of these tags, the neurons still found each other and wired up normally, suggesting the wiring system has built-in backup so that losing one piece doesn't break the whole circuit; however, removing one of the proteins did affect how many connection points (synapses) the neurons formed. We also found that similar patterns of these genes show up in mosquitoes and ants, hinting that this molecular tagging strategy for wiring the brain's smell circuits is an ancient, evolutionarily conserved trick shared across insects. Overall, the work adds an important piece to the puzzle of how brains reliably wire themselves up correctly during development, a question relevant well beyond flies.

This fruit fly visual system has roughly 250 distinct types of neurons, and this work asks a basic question: how does each neuron "know" what type of cell to become, and how does it then carry out the elaborate genetic program that makes it look and function differently from its neighbors? Scientists have known that each neuron type relies on its own distinctive combination of "terminal selector" proteins, a set of master-switch regulators that turn genes on and off, but exactly how those combinations get set up during development, and how they then control each neuron's gene activity, was largely a mystery.

To find out, we used a powerful technique that simultaneously reads out both which genes are switched on and which stretches of DNA are open and accessible for regulation, in more than 230,000 individual brain cells collected at four stages of fly development, from early construction to full adulthood. This lets us build a detailed atlas linking each neuron type to the specific DNA "control switches" (enhancers) it uses and the combinations of regulatory proteins that flip those switches. We found that the genetic control system is highly dynamic and cell-specific: the same master regulator proteins can act through completely different DNA switches depending on the neuron type and its developmental stage, and a critical early window shortly after a neuron is born appears to lock in its regulatory identity before the neuron matures further. Beyond satisfying basic curiosity about how brains build their staggering cellular diversity from a limited starting set of stem cells, this work provides a detailed genetic blueprint that could help researchers understand principles of brain wiring likely shared across many species, since flies are a well-established model for studying nervous system development.

A central challenge in evolutionary neuroscience is understanding how neural circuits diversify to produce species-specific behaviors while retaining conserved architecture. This question is especially relevant in Drosophila, where closely related species display striking differences in male courtship despite sharing similar brain structures and genetic programs. Sexual circuits labeled by doublesex (dsx⁺) neurons provide a powerful model for addressing this gap, yet the field has lacked a high-resolution, cross-species comparison of their cellular composition and molecular identities. We set out to determine which aspects of dsx⁺ circuits are evolutionarily conserved, which features diverge, and how these changes might underlie behavioral diversification.

Using high-resolution single-cell transcriptomics across four Drosophila species, the study identifies 84 distinct dsx⁺ neuron types and reveals that the overall cellular architecture of sexual circuits is deeply conserved, with minimal gain or loss of cell types over evolution. However, transcriptomic comparisons uncover extensive heterogeneity in how these conserved neuron types diverge. Core identity features—such as fruitless expression, neurotransmitter and monoamine usage, and key transcription factors—remain stable, whereas neuropeptide signaling pathways show dramatic, cell-type-specific evolutionary turnover. These results suggest that behavioral diversification arises not from reshaping circuit structure but from fine-scale molecular remodeling within conserved cell types. We further show that male-specific neurons are not disproportionately divergent and provide an online resource for exploring cell-type-specific markers, establishing a foundational framework for studying the evolutionary basis of behavioral adaptation.

A major gap in developmental neuroscience has been the lack of genetic tools that can specifically and stably label distinct neuronal lineages throughout development and into adulthood. This limitation has made it difficult to study how neurons assemble into functional circuits and contribute to behavior over time, especially in complex nervous systems like that of the fruit fly, Drosophila melanogaster.

This study fills that gap by creating a large library of split-GAL4 driver lines that target individual hemilineages—developmentally related groups of neurons—in the fly’s ventral nerve cord. These genetically engineered lines remain active across developmental stages, allowing us to visualize how neuronal morphology changes, identify neurotransmitter profiles, and activate specific lineages using optogenetics. By linking each hemilineage to particular behaviors, we provide a powerful framework for exploring how neural circuits are built and function from development to adulthood.

In the brain, different layers of neurons connect with specific partners to perform precise functions. In the visual system of fruit flies, certain neurons called T4 and T5 specialize in detecting motion and send their signals to specific layers where they connect with other neurons. In this collaborative work with Pinto-Teixeira’s group, we discovered that cell adhesion molecules called Beat and Side, which help cells stick together, play a key role in ensuring these neurons connect in the correct layers. By studying how these proteins work during development, we found that they do not directly create the connections between neurons. Instead, they help neurons group into the right layers, ensuring they are close enough to form the correct connections later. This process creates highly organized and accurate wiring in the brain, allowing neurons to communicate with the right partners and perform their specialized roles.

Drosophila has multiple taste organs throughout the body to detect chemicals that signal palatability or noxious quality. It is still unclear how individual neurons in each taste organ act to control feeding. Here, we use the fly pharynx as a model to study the extent to which taste information is integrated at the cellular level to regulate the consumption of sugars and amino acids. We generate a taste-blind fly and establish a critical role of pharyngeal input in food selection. We also study the feeding behavior of flies in which only selected pharyngeal neurons are restored and show examples of taste integration as well as redundancy in how pharyngeal neurons control the overall consumption of sugars and amino acids.

Understanding the role of spontaneous activity in the developing nervous system has been advancing rapidly due to a wealth of sophisticated genetic and optogenetic tools and imaging techniques. In this review, we present the current knowledge of the molecular and cellular mechanisms underlying spontaneously emerging coordinated neuronal activity in the developing visual system of both vertebrates and invertebrates. We compare the conceptual similarities between the waves of activity in the developing vertebrate and invertebrate visual systems and propose Drosophila as a powerful model system to investigate important questions related to this general developmental phenomenon.

In addition to an understanding of how tastants of five basic taste modalities (sweet, bitter, acids, salts, and amino acids) are sensed, findings in recent years in Drosophila have identified taste neurons or receptors involved in detecting tastants of non-canonical modalities, including fatty acids, carbonation, polyamines, ammonia, calcium, and H2O2/bacterial lipopolysaccharides. In this review, we present a timely overview of the molecular and cellular basis of taste detection in Drosophila. We also summarize evidence for organotopic and multimodal functions of the taste system, which are of interest to the fields of both insect feeding regulation and mammalian taste.

Pharyngeal taste organs have been long assumed to as act a gatekeeper for monitoring food quality and controlling ingestion, but the functional evidence is lacking. Here we show how pharyngeal taste neurons drive the evaluation and feeding avoidance of different aversive tastants via a combinatorial sensory coding strategy. Notably, researchers have often overlooked at pharyngeal taste organs when interpreting results of feeding behavior experiments. Our findings not only make basic contributions to the fields of taste biology and regulation of insect feeding behavior but also have an impact on strategies for developing anti-feedants as part of integrated insect management strategies. 


Animals control food intake to meet their nutritional need and avoid toxic compounds in their environment. Such feeding control is tightly regulated through orchestrating the sensory-motor neuronal circuits. However, the neuronal circuits underlying individual feeding behaviors have yet to be elucidated. Here we screened ~200 GAL4 lines for neurons controlling feeding behaviors and found one line (VT041723-GAL4) that labels neurons receiving pharyngeal taste input and controlling regurgitation. This study act as a starting point for dissecting the regurgitation circuits, and a better understanding of feeding neuronal circuits will provide a novel design in controlling insect pests.

Pox-neuro (Poxn) mutants have been widely used in Drosophila gustation research. In these mutants, all external taste hairs are transformed into mechanosensory hairs, offering a tool with which to identify taste-enriched genes and investigate behavioral consequences of ablating taste input. However, recent work indicates that chemoreceptor expression and function are likely intact in internal pharyngeal taste organs in Poxn mutants. Here, we present the advantages and shortcomings of using Poxn mutants in gustation research and reevaluate some of the established conclusions derived from previous work with these mutants. We also discuss the use of Poxn mutants for studying pharyngeal taste.

In Drosophila, most gustation research has focused on neurons residing in external taste hairs in the labellum, legs, and wing margins. There remains a complex repertoire of pharyngeal taste neurons lying in an anatomical position to control food intake, which has been largely overlooked. In this study, I carried out a large-scale, systematic analysis of the molecular organization of pharyngeal taste neurons, and established a detailed receptor-to-neuron map for all pharyngeal taste neurons. The detailed map contributes to the development of a minimal taste system model where only pharyngeal GRNs are being manipulated and to the study of the roles of each pharyngeal GRNs in feeding control.

Much is known about sugar sensing through peripheral sweet taste neurons in the fly’s legs and labellum. However, sugar sensing by the pharyngeal taste organs has remained unexplored due to their inaccessibility to electrophysiology and the lack of genetic tools to specifically manipulate their function. Here, we characterize the physiological and behavioral roles of pharyngeal sweet taste neurons and identify a subset of gustatory receptor genes that are expressed in these neurons. We also show that mutant flies lacking all external taste hairs are nevertheless capable of selecting sugars by virtue of pharyngeal taste neurons, providing direct functional evidence of pharyngeal taste neurons.

Following our previous Syt I work, we further show that adenosine receptor is expressed in wave-initiating neurons, and adenosine signaling up-regulates the frequency of retinal waves. Retinal waves propagate through the developing retina, inducing similar burst patterns in the thalamus and visual cortex to form sensory loops. The etiology of schizophrenia and autism has been attributed to a developmental disorder of neural connectivity in the formation of sensory maps. Thus, identifying the roles of exocytotic or neuromodulator molecules that regulate the properties of retinal waves in developing neural circuits would help developing novel therapeutic methods for human psychiatric diseases.

During a developmental critical period, the spontaneous bursts of action potentials fire periodically and propagate across a population of developing retinal neurons to refine the visual circuits, termed as “retinal waves”. However, how retinal waves occur and how they are regulated remain mysterious. Here we show that the firing patterns of retinal waves can be modulated by a calcium sensor protein (Synaptotagmin I, Syt I) expressing in the wave-initiating neurons. We also show that the two calcium-binding domains of Syt I regulate the temporal properties of retinal waves during development. In this study, we also developed an in vitro electroporation method for gene delivery into retinas.

This commentary discusses a Journal of Neuroscience article published by Dr. Nirupa Chaudhari’s group. We provide a short overview of the topic and questions addressed in the commented paper, a critical review of the key findings, and a brief summary of the significance of the paper. We place this in the context of a broader picture of diverse cellular and molecular mechanisms of salt taste transduction among different taste cell types. We raise an interesting parallel with Drosophila sweet-sensing neurons in responding to high salt that could have some interesting implications for taste coding. We also point out the potential inhibitory role of K+ in salt taste transduction.

This research highlight discusses a Cell Research article published by Dr. Liming Wang’s group. We summarize the known cellular and molecular pathways involved in sensing amino acids in Drosophila and point out the diverse role of DH44 neuroendocrine cells in the Drosophila brain in sensing both sugars and amino acids. We propose a compelling brain-gut microcircuit that senses sugars and amino acids and promotes food intake through DH44 signaling and raising several interesting questions about the cellular and molecular mechanisms integrating information about both sugars and amino acids for balancing nutrient intake with metabolic needs. 


This commentary discusses a Journal of Neuroscience article published by Dr. Dean Smith’s group. We provide a short overview of the olfactory adaptation and performed a critical analysis of the commented papers. We raise a model of how olfactory responses by odorant coreceptor (Orco) phosphorylation are modulated over time. Given that a screening system for small molecules that target phosphorylation-dependent protein–protein interaction has been established, we also propose modulation of olfactory responses by the phosphorylation status of Orco could lead to the discovery of new generations of insect repellents against insect vectors and agricultural pests.

This commentary discusses a Journal of Neuroscience article published by Dr. Marla Feller’s group. I summarize the mechanisms underlying the activity-dependent modulation of intrinsically photosensitive retinal ganglion cells (ipRGCs) gap junction networks in the developing retina. I raise several interesting future directions, such as identifying subtypes of ipRGCs, characterizing their light responses, and determining which subtypes are coupled and which are not. I also place it in the context of other recent work in the visual cortex and propose that the activity-dependent regulation of gap junction coupling networks might be a conserved feature in the developing nervous systems.

This commentary discusses a Journal of Neuroscience article published by Dr. Frédéric Marion-Poll’s group. To promote behavioral avoidance, bitter compounds have been proposed to not only activate bitter taste neurons but also inhibit sweet taste neurons. Here, I summarize different mechanisms that bitter compounds can mask the sweetness in food mixture in Drosophila. I raise future directions to study how previously identified GABAergic interneurons inhibit sweet taste neurons. Since the suppression of sweet taste by bitter compounds has been observed in other insects, a better understanding of its underlying mechanism could be used for designing novel feeding deterrents for insect pests.