Biology subjects

Rayes, D.

Publications and source records attributed to Rayes, D..

9 recordsLinked to original sources

bioRxiv2026

Microexon alternative splicing and feeding behavior in C. elegans.

Microexons are short alternative exons up to 51 nucleotides long that are highly enriched in neuronal genes. Their dysregulation has been linked to human neurodevelopmental disorders, including autism spectrum disorders. In the nematode Caenorhabditis elegans, global regulation of microexons is also critical for proper development. Here we show that microexon alternative splicing (AS) changes between C. elegans larval and adult stages and that microexon inclusion is differentially regulated among distinct neuronal types. Consistently with previous evidence that C. elegans splicing is regulated in response to environmental stimuli, we found here that specific microexons are modulated upon food availability. Both the inclusion levels of these microexons and the feeding behavior seem to depend on the DNA topology, which may affect transcription dynamics, as revealed by the effects of the topoisomerase I (TOP1) inhibitor, camptothecin (CPT). CPT treatment alters responses related to food availability such as speed reduction and exploration. Furthermore, animals carrying a mutation in the global regulator of microexon splicing prp-40 exhibit altered food preference, independently demonstrating that disruption of microexon AS has important consequences on animal behavior.

molecular biology↗

bioRxiv2025

Cytoplasmic TDP-43 leads to early functional impairments without neurodegeneration in a Serotonergic Neuron-Specific C. elegans Model

TDP-43 proteinopathies, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are marked by the pathological cytoplasmic accumulation of TAR DNA-binding protein 43 (TDP-43), leading to progressive neuronal dysfunction and degeneration. To investigate the early functional consequences of TDP-43 mislocalization, we generated Caenorhabditis elegans models expressing either wild-type human TDP-43 or a variant with a mutated nuclear localization signal ({Delta}NLS), specifically in serotonergic neurons. These neurons were chosen because i) serotonin deficits are a feature of ALS/FTD and ii) in C. elegans, they regulate well-characterized behaviors, providing a straightforward readout of neuronal function. We found that expression of either TDP-43 variant impaired serotonin-dependent behaviors--including pharyngeal pumping, egg-laying, and locomotion slowing upon food encounter--with the cytoplasmic {Delta}NLS form causing more severe deficits. Serotonergic neurons remained i) morphologically intact, indicating that neuronal dysfunction precedes overt neurodegeneration; and ii) partially responsive to the selective serotonin reuptake inhibitor fluoxetine, suggesting that neurotransmitter release is still partially functional. Altogether, our findings demonstrate that cytoplasmic TDP-43 disrupts neuronal signaling and behavior early in disease progression. This C. elegans model provides a genetically tractable system to dissect early mechanisms of TDP-43-mediated dysfunction and to identify therapeutic strategies targeting predegenerative stages of ALS/FTD.

neuroscience↗

bioRxiv2024

Fluorescent-based sex-separation technique in major invasive crop pest, Drosophila suzukii

Insect population biocontrol methods such as the sterile insect technique (SIT), represent promising alternatives to traditional pesticide-based control applications. To use these strategies efficiently requires scalable sex separation techniques which are currently lacking in Drosophila suzukii, a prominent crop pest species. Having previously characterized a fluorescence-based sex-sorting technique in other pests, termed SEPARATOR (Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter), here we explore its potential applicability to Drosophila suzukii. Here, we engineer several strains of Drosophila suzukii encoding SEPARATOR constructs that allow for efficient sex selection in early larval stages.

genetics↗

bioRxiv2024

The neurohormone tyramine stimulates the secretion of an Insulin-Like Peptide from the intestine to modulate the systemic stress response in C. elegans

The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, lifespan, and stress resistance. In C. elegans, DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood. Here, we show that the ILP, INS-3, plays a crucial role in modulating the response to different types of stressors in C. elegans. ins-3 mutants display increased resistance to both heat and oxidative stress; however, under favorable conditions, this advantage is countered by slower reproductive development. ins-3 expression in both neurons and the intestine is downregulated in response to environmental stressors. Conversely, the neurohormone tyramine, which is released during the acute flight response, triggers an upregulation in ins-3 expression. Moreover, we found that tyramine negatively impacts environmental stress resistance by stimulating the release of INS-3 from the intestine. The subsequent release of INS-3 systemically activates the DAF-2 pathway, resulting in the inhibition of cytoprotective mechanisms mediated by DAF-16/FOXO and HSF-1. These studies offer mechanistic insights into the brain-gut communication pathway that weighs adaptive strategies to respond to acute and long-term stress scenarios.

neuroscience↗

bioRxiv2023

A fluorescent sex-sorting technique for insects with the demonstration in Drosophila melanogaster

Recent advances in insect genetic engineering offer alternative genetic biocontrol solutions to control populations of pests and disease vectors. While success has been achieved, sex-sorting remains problematic for scaling many genetic biocontrol interventions. Here we describe the development of a sex-sorting technique for female and male selection with a proof-of-concept in D. melanogaster termed SEPARATOR (Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter). This approach utilizes dominant fluorescent proteins and differentially spliced introns to ensure sex-specific expression. The system has the potential for adaptability to various insect species and application for high-throughput insect sex-sorting.

genetics↗

bioRxiv2023

The Ketone body beta-hydroxybutyrate rescues GABAergic defects in C. elegans daf-18/PTEN mutants

A finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including Autism Spectrum Disorders (ASDs). Mutations in PTEN, the main negative regulator of the PI3K/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using the C. elegans neuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found that daf-18/PTEN mutations specifically impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The specific defects observed in the GABAergic system in daf-18/PTEN mutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body {beta}-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function in daf-18/PTEN mutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs. Highlights*daf-18/PTEN deficiency in C. elegans results in a specific impairment of inhibitory GABAergic signaling, while the excitatory cholinergic signaling remains unaffected. *The dysfunction of GABAergic neurons in these mutants arises from the inactivity of the transcription factor DAF-16/FOXO during their development, resulting in conspicuous morphological and functional alterations. *A diet enriched with the ketone body {beta}-hydroxybutyrate, which induces DAF-16/FOXO activity, mitigates the functional and morphological defects in the development of GABAergic neurons *{beta}-hydroxybutyrate supplementation during the early stages of development is both necessary and sufficient to achieve these rescuing effects on GABAergic signaling in daf-18/PTEN mutants. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/535850v4_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@12e5ab8org.highwire.dtl.DTLVardef@45f1eborg.highwire.dtl.DTLVardef@daebborg.highwire.dtl.DTLVardef@4a8d95_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

Gain-of-function mutations in the UNC-2/CaV2α channel lead to hyperactivity and excitation-dominant synaptic transmission in Caenorhabditis elegans

Mutations in pre-synaptic voltage gated calcium channels can lead to familial hemiplegic migraine type 1 (FHM1). While mammalian studies indicate that the migraine brain is hyperexcitable due to enhanced excitation or reduced inhibition, the molecular and cellular mechanisms underlying this excitatory/inhibitory (E/I) imbalance are poorly understood. We identified a gain-of-function (gf) mutation in the Caenorhabditis elegans CaV2 channel 1 subunit, UNC-2, which leads to increased calcium currents. unc-2(gf) mutants exhibit hyperactivity and seizure-like motor behaviors. Expression of the unc-2 gene with FHM1 substitutions R192Q and S218L leads to hyperactivity similar to that of unc-2(gf) mutants unc-2(gf) mutants display increased cholinergic- and decreased GABAergic-transmission. Moreover, we reveal that and increased cholinergic transmission in unc-2(gf) mutants leads to reduction of GABA synapses in a TAX-6/calcineurin dependent manner. Our studies provide mechanistic insight into how CaV2 gain-of-function mutations disrupt excitation-inhibition balance in the nervous system.

neuroscience↗

bioRxiv2018

Acute-stress impairs cytoprotective mechanisms through neural inhibition of the insulin pathway

Persistent activation of the \"fight-or-flight\" response accelerates aging and increases the susceptibility to disease. We show that repeated induction of the C. elegans flight response inhibits conserved cytoprotective mechanisms. This acute-stress response activates neurons that release tyramine, the invertebrate analog of adrenaline/noradrenaline. Tyramine stimulates the DAF-2/Insulin/IGF-1 pathway and precludes the nuclear translocation of the DAF-16/FOXO transcription factor through the activation of an adrenergic-like receptor TYRA-3 in the intestine. In contrast, environmental long-term stressors, such as heat or oxidative stress, reduce tyramine release allowing the induction of FOXO-dependent cytoprotective genes. These findings demonstrate how a neural stress-hormone signaling provides a state-dependent neural switch between acute and long-term stress responses, and provide mechanistic insights how acute stress impairs cellular defensive systems.\n\nOne Sentence Summary: The \"fight-or-flight\" response reduces resistance to environmental challenges.

neuroscience↗

bioRxiv2018

Co-option of neurotransmitter signaling for inter-organismal communication in C. elegans

Biogenic amine neurotransmitters play a central role in metazoan biology, and both their chemical structures and cognate receptors are evolutionarily conserved. Their primary roles are in intra-organismal signaling, whereas biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in C. elegans, a neurotransmitter-sensing G protein-coupled receptor, TYRA-2, is required for avoidance responses to osas#9, an ascaroside pheromone that incorporates the neurotransmitter octopamine. Neuronal ablation, cell-specific genetic rescue, and calcium imaging show that tyra-2 expression in the nociceptive neuron ASH is necessary and sufficient to induce osas#9 avoidance. Ectopic expression in the AWA neuron, which is generally associated with attractive responses, reverses the response to osas#9, resulting in attraction instead of avoidance behavior, confirming that TYRA-2 partakes in sensing osas#9. The TYRA-2/osas#9 signaling system thus represents an inter-organismal communication channel that evolved via co-option of a neurotransmitter and its cognate receptor.

neuroscience↗