Biology subjects

Tadres, D.

Publications and source records attributed to Tadres, D..

5 recordsLinked to original sources

bioRxiv2026

Unilateral gene expression via maternally controlled zygotic recombination in Drosophila

Structural and functional asymmetries are ubiquitous in bilaterians, but tools for unilateral genetic access have been lacking, a methodological gap that has limited mechanistic dissections of lateralized cellular functions. We developed the Maternally Controlled Zygotic Recombination (MCZR) system to overcome this limitation in Drosophila, co-opting the regulatory machinery of the maternal-to-zygotic transition to enable somatic recombination during early embryonic development. Targeting recombinase activity to this early window generates large somatic mosaics that frequently split across the anatomical midline. In conjunction with cell type-specific driver lines, this approach provides a reliable, scalable, and user-friendly platform for unilateral transgene expression. In proof-of-concept experiments, we apply our tool to the question of locomotor control, illustrating how MCZR can be used to unilaterally manipulate or monitor a cell type of interest. Overall, the MCZR system unlocks previously inaccessible experimental avenues across neuroscience, cell biology, and developmental biology.

neuroscience↗

bioRxiv2025

Neuronal silencing through depolarization block underlies odor discrimination

The olfactory system enables animals to distinguish between attractive and aversive odor sources through the perception of odorant molecules. A fundamental challenge is maintaining stable odor identity perception despite fluctuating stimulus intensities during navigation. Using the numerically simple olfactory system of the Drosophila larva, we combined a quantitative odor discrimination assay, electrophysiology, computational modelling, and ectopic expression of odorant receptors to study the encoding of odor identity. We found that depolarization block, which silences olfactory sensory neurons (OSNs) at odor concentrations 3-4 log units above the detection threshold, enables odor discrimination by creating distinct patterns of OSN activity. In a minimal system with two functional OSNs, larvae discriminate between odors when depolarization block creates differential OSN silencing but fail to distinguish odors producing qualitatively similar activity patterns in both OSNs. This principle extends to odor mixtures and the fully functional olfactory system, where the high affinity of the OR42b odorant receptor for one of the test odors enables discrimination regardless of which OSN expresses OR42b. Our results indicate that depolarization block serves as an integral feature of olfactory coding alongside combinatorial OSN activation. Selective silencing of high-affinity OSNs creates distinct neural representations and enables discrimination between odors that would otherwise produce similar activity patterns. This mechanism appears evolutionarily conserved across sensory systems, from olfactory sensory neurons to photoreceptors, suggesting that selective neuronal silencing serves as a mechanism for maintaining distinct sensory representations across stimulus intensities.

neuroscience↗

bioRxiv2024

Odorant receptors tuned to isothiocyanates in Drosophila melanogaster and their evolutionary expansion in herbivorous relatives

Plants release defense volatile compounds that can deter herbivores. Among them are electrophilic toxins, such as isothiocyanates from mustard plants, that activate pain receptors by contact (i.e. taste) in many animals, including Drosophila melanogaster. While specialist insects have evolved strategies to tolerate toxicity and use mustard plants as hosts, it is unclear whether non-specialist insects detect and avoid electrophilic toxins via olfaction. To address this, and to understand if specialized insects co-opted these toxic compounds as hostplant olfactory cues, we leveraged closely related drosophilid species, including the microbe-feeding D. melanogaster and Scaptomyza pallida, and the mustard-feeding specialist S. flava. In olfactory assays, D. melanogaster exposed to allyl isothiocyanate volatiles were rapidly immobilized, demonstrating the high toxicity of this wasabi-derived compound to non-specialists. Through single sensillum electrophysiological recordings from olfactory organs and behavioral assays, we identified an Olfactory receptor (Or) necessary for volatile detection and behavioral aversion to allyl isothiocyanate in D. melanogaster. RNA sequencing and heterologous expression revealed that S. flava possess lineage-specific, triplicated homologs of this Or, and that each paralog exhibited broadened and distinct sensitivity to isothiocyanate compounds. Using AlphaFold2 modeling, site-directed mutagenesis and electrophysiological recordings, we identified two critical amino acid substitutions that changed the sensitivity of these paralogs from fruit-derived odors to isothiocyanates in the mustard specialist S. flava. Our findings show that non-specialists can detect electrophiles via olfaction, and that their olfactory systems can rapidly adapt to toxic hostplant niches through co-option and duplication of ancestral chemosensory genes with few amino acid changes.

evolutionary biology↗

bioRxiv2022

An essential experimental control for functional connectivity mapping with optogenetics

To establish functional connectivity between two candidate neurons that might form a circuit element, a common approach is to activate an optogenetic tool such as Chrimson in the candidate pre-synaptic neuron and monitor fluorescence of the calcium-sensitive indicator GCaMP in a candidate post-synaptic neuron. While performing such experiments, we found that low levels of leaky Chrimson expression can lead to strong artifactual GCaMP signals in presumptive postsynaptic neurons even when Chrimson is not intentionally expressed in any particular neurons. Withholding all-trans retinal, the chromophore required as a co-factor for Chrimson response to light, eliminates GCaMP signal but does not provide an experimental control for leaky Chrimson expression. Leaky Chrimson expression appears to be an inherent feature of current Chrimson transgenes, since artifactual connectivity was detected with Chrimson transgenes integrated into three different genomic locations (two insertions tested in larvae; a third insertion tested in the adult fly). These false-positive signals may complicate the interpretation of functional connectivity experiments. We illustrate how a no-Gal4 negative control improves interpretability of functional connectivity assays. We also propose a simple but effective procedure to identify experimental conditions that minimize potentially incorrect interpretations caused by leaky Chrimson expression.

neuroscience↗

bioRxiv2019

PiVR: an affordable and versatile closed-loop platform to study unrestrained sensorimotor behavior

Tools enabling closed-loop experiments are crucial to delineate causal relationships between the activity of genetically-labeled neurons and specific behaviors. We developed the Raspberry Pi Virtual Reality system (PiVR) to conduct closed-loop optogenetic stimulation of neural functions in unrestrained animals. PiVR is an experimental platform that operates at high-temporal resolution (>50 Hz) with low latencies (~10 ms), while being affordable (<$500) and easy to build (<6 hours). This tool was designed to be accessible to a wide public, from highschool students to professional researchers studying systems neuroscience. We illustrate the functionality of PiVR by focusing on sensory navigation in response to gradients of chemicals (chemotaxis) and light (phototaxis). We show how Drosophila flies perform negative chemotaxis by modulating their locomotor speed to avoid locations associated with optogenetically-evoked bitter taste. In Drosophila larvae, we use innate positive chemotaxis to compare orientation behavior elicited by real- and virtual-odor gradients with static shapes as well as by turbulent virtual-odor plumes. Finally, we examine how positive phototaxis emerges in zebrafish larvae from the modulation of turning maneuvers during the ascent of virtual white-light gradients. Besides its application to study chemotaxis and phototaxis, PiVR is a versatile tool designed to bolster efforts to map and to functionally characterize neural circuits.

neuroscience↗