Biology subjects

Laurent, P.

Publications and source records attributed to Laurent, P..

9 recordsLinked to original sources

bioRxiv2025

Opposing roles for lipocalins and a CD36 family scavenger receptor in apical extracellular matrix-dependent protection of narrow tube integrity

All exposed epithelial surfaces, including the walls of internal tubes, are lined by a lipid and glycoprotein-rich apical extracellular matrix (aECM) that helps shape and protect the apical domain. Secreted lipocalins are lipid transporters frequently found within apical compartments. We show that loss of the C. elegans lipocalin LPR-1 disrupts the assembly of another lipocalin, LPR-3, within the pre-cuticle aECM that protects and shapes the narrow excretory duct and pore tubes. LPR-1 is apically secreted and colocalizes with LPR-3 in intracellular vesicles and lysosomes, but unlike LPR-3 it does not detectably incorporate into the aECM. Forward genetic screens for lpr-1 suppressors identified mutations in scav-2, which encodes a transmembrane protein of the CD36 scavenger receptor B family. Loss of scav-2 restored LPR-3 matrix localization and suppressed the lpr-1 tube shaping defect, as well as the tube-shaping defects of a subset of pre-cuticle mutants, but not lpr-3 mutants. A SCAV-2 fusion accumulated at apical surfaces of interfacial epithelial tubes, including the excretory duct and pore, and both tissue-specific suppression of lpr-1 matrix defects and tissue-specific rescue experiments support a local role for SCAV-2 within these tubes. These data demonstrate that LPR-1 and SCAV-2 have opposing effects on narrow tube integrity by altering the content and organization of that tubes luminal aECM, possibly by acting as transporters of an LPR-3 cofactor. These results have broadly relevant implications regarding the importance of lipocalins and scavenger receptors for aECM organization and integrity of the narrowest tubes in the body.

cell biology↗

bioRxiv2025

Sensory stimuli and cilium trafficking defects trigger the release of ciliary extracellular vesicles from multiple ciliary locations

The primary cilium is a signaling organelle that extends from many cell types to detect and relay extracellular signals. Beyond its signaling role, the cilium also produces cilia-derived extracellular vesicles (cEVs), although the mechanisms underlying their biogenesis and functions remain poorly understood. We characterized the cEV biogenesis in vivo using ciliated sensory neurons of C. elegans. In response to sensory cues, interruption of the intraflagellar transport (IFT) -a ciliary trafficking machinery carrying cargoes along the cilium-occurs together with ciliary membrane fission, resulting in the release of cEVs. Similarly, mutants disrupting IFT and ciliary receptor trafficking also enhance cEV production. To investigate how IFT influences the rate and location of cEV biogenesis, we selected a membrane marker that spans the entire length of the ciliary membrane independently of IFT. Single-molecule tracking demonstrates that the tetraspanin TSP-6 enters and diffuses within the cilia and does it independently of IFT. Lack of receptor retrieval or receptor entry in the cilium induces membrane budding from ciliary or periciliary membranes, respectively. Prior to fission, these membrane buds get enriched in TSP-6 as well as signaling receptors. Coupling receptor buildup with their export by cEVs provides a mechanism to preserve ciliary function and to modulate ciliary signaling. HIGHLIGHTS- The cone-shaped tetraspanin TSP-6 crosses the transition zone and moves by passive diffusion within the ciliary membrane, independently of IFT. - The production of ciliary EVs loaded with TSP-6 increases upon acute sensory stimulation or when IFT of ciliary membrane proteins is disrupted. - Depending on the nature of the perturbations, ciliary EVs remove excess material from the distal, proximal or periciliary segments of the cilia.

cell biology↗

bioRxiv2024

A Blueprint of Sex-Specific Neuronal Regulation in the C. elegans Nervous System at Single-Cell Resolution

Sex-specific behaviors are often attributed to differences in neuronal wiring and molecular composition, yet how genetic sex shapes the molecular architecture of the nervous system at the individual neuron level remains unclear. Here, we use single-cell RNA sequencing to profile the transcriptome of sex-shared neurons in adult Caenorhabditis elegans males and hermaphrodites. We uncover widespread molecular dimorphism across the nervous system, including in previously unrecognized neuron-types such as the touch receptors. Neuropeptides and signaling-related genes exhibit strong sex-biased expression, particularly in males, reinforcing the notion that neuropeptides are crucial for diversifying connectome outputs. Despite these differences, neurotransmitter identities remain largely conserved, indicating that functional dimorphism arises through modulatory, not identity-defining, changes. We show that sex-biased expression of neurotransmitter-related genes correlates with bias in outgoing synaptic connectivity and identify regulatory candidates for synaptic wiring, including both shared and sex-specific genes. This dataset provides a molecular framework for understanding how subtle regulatory differences tune conserved circuits to drive sex-specific behaviors.

neuroscience↗

bioRxiv2023

Acute avoidance of hydrogen sulfide is modulated by external and internal states in C. elegans

Hydrogen sulfide (H2S) acts as an energy source, a toxin, and a gasotransmitter across diverse biological contexts. We use the robust locomotory responses of Caenorhabditis elegans to high levels of H2S to elucidate the molecular mechanisms underlying its acute and adaptive responses. We find that the H2S-evoked behavioral response is shaped by multiple environmental factors including oxygen (O2) levels and nutritional state, and is modulated by various pathways such as insulin, TGF-{beta}, and HIF-1 signaling, as well as by input from O2-sensing neurons. Prolonged exposure to H2S activates HIF-1 signaling, leading to the upregulation of stress-responsive genes, including those involved in H2S detoxification. This promotes an adaptive state in which locomotory speed is reduced in H2S, while responsiveness to other stimuli is preserved. In mutants deficient in HIF-1 signaling, iron storage, and detoxification mechanisms, animals display a robust initial response but rapidly enter a sleep-like behavior characterized by reduced mobility and diminished responsiveness to subsequent sensory stimuli. Furthermore, while acute production of mitochondria-derived reactive O2 species (ROS) appears to initiate the avoidance response to H2S, persistently high ROS promotes an adaptive state, likely by activating various stress-response pathways, without substantially compromising cellular H2S detoxification capacity. Taken together, our study provides comprehensive molecular insights into the mechanisms through which C. elegans modulates and adapts its response to H2S exposure.

animal behavior and cognition↗

bioRxiv2021

Ectosome uptake by glia sculpts Caenorhabditis elegans cilia

Cilia are sensory organelles protruding from cell surface. A tight regulation of membrane receptors traffic in and out of cilia is achieved by the action of Intraflagellar Transport (IFT). Here, we show that ectosomes bud from a subset of C. elegans sensory cilia. Packing and disposal of ciliary receptors in ectosomes complement their retrieval by IFT. Mutations in ciliary retrieval genes increase export of the salt sensor GCY-22 from ASER neurons by ectosomes, preventing its accumulation in ASER cilia. Ectosomes are produced from two ciliary locations: cilia tip and/or cilia base. Ectosomes budding from cilia tip are released in the environment. Ectosomes produced from the cilia base are concomitantly phagocytosed by the associated glial cells. Although ectocytosis does not require glia to occur, ectosome phagocytosis by the contacting glia contributes to maintain cilia shape and sensory function. We suggest this coordinated neuron-glia interaction is required for proper cilia function.

cell biology↗

bioRxiv2020

Constructing neural network models from brain data reveals representational transformations underlying adaptive behavior

The human ability to adaptively implement a wide variety of tasks is thought to emerge from the dynamic transformation of cognitive information. We hypothesized that these transformations are implemented via conjunctive activations in conjunction hubs - brain regions that selectively integrate sensory, cognitive, and motor activations. We used recent advances in using functional connectivity to map the flow of activity between brain regions to construct a task-performing neural network model from fMRI data during a cognitive control task. We verified the importance of conjunction hubs in cognitive computations by simulating neural activity flow over this empirically-estimated functional connectivity model. These empirically-specified simulations produced above-chance task performance (motor responses) by integrating sensory and task rule activations in conjunction hubs. These findings reveal the role of conjunction hubs in supporting flexible cognitive computations, while demonstrating the feasibility of using empirically-estimated neural network models to gain insight into cognitive computations in the human brain.

neuroscience↗

bioRxiv2019

Combining single-cell RNA-sequencing with a molecular atlas unveils new markers for C. elegans neuron classes.

Single-cell RNA-sequencing (scRNA-seq) of the Caenorhabditis elegans (C. elegans) nervous system offers the unique opportunity to obtain a partial expression profile for each neuron within a known connectome. Building on recent scRNA-seq data [1] and on a molecular atlas describing the expression pattern of ~800 genes at the single cell resolution [2], we designed an iterative clustering analysis aiming to match each cell-cluster to the ~100 anatomically defined neuron classes of C. elegans. This heuristic approach successfully assigned 58 clusters to their corresponding neuron class. Another 11 clusters grouped neuron classes sharing close molecular signatures and 7 clusters were not assigned. Based on these 76 molecular profiles, we designed 15 new neuron class-specific promoters validated in vivo. Amongst them, 10 represent the only specific promoter reported to this day, expanding the list of neurons amenable to genetic manipulations. Finally, we observed a differential expression of functionally relevant genes between sensory-, inter-, and motor neurons in C. elegans, suggesting the mode of functional diversification may vary accordingly to the neuronal modalities.

genetics↗

bioRxiv2019

Multidimensional phenotyping predicts lifespan and quantifies health in C. elegans

Ageing affects a wide range of phenotypes at all scales, but an objective measure of ageing remains challenging, even in simple model organisms. We assumed that a wide range of phenotypes at the organismal scale rather than a limited number of biomarkers of ageing would best describe the ageing process. Hundreds of morphological, postural and behavioural features are extracted at once from high resolutions videos. A quantitative model using this multi-parametric dataset can predict the biological age and lifespan of individual C. elegans. We show that the quality of predictions on a held-out data set increases with the number of features added to the model, supporting our initial hypothesis. Despite the large diversity of ageing mechanisms, including stochastic insults, our results highlight a robust ageing trajectory, but variable ageing rates along that trajectory. We show that healthspan, which we defined as the range of abilities of the animals, is correlated to lifespan in wild-type worms.

systems biology↗

bioRxiv2019

Deep behavioural phenotyping reveals divergent trajectories of ageing and quantifies health state in C. elegans

Neurodegenerative diseases may be the cause or the consequence of an acceleration of physiological ageing. Evidence for this concept is lacking due to practical limitations of human studies. Here, we compared the processes of physiological and pathological ageing of individual C. elegans over their lifespan. Using multi-parametric phenotyping, trajectories of ageing can be defined within a phenotypic landscape made of a large set of phenotypical features. Rather than an acceleration of ageing, a model for synucleinopathy showed a divergent trajectory of ageing. The pathological progression in individual animals can be predicted from early phenotypes with high accuracy. Despite of similar lifespans, disease-model worms display an early onset of decline in their phenotypic range of ability. This loss of flexibility provides an index of health valid for physiological and pathological contexts. Finally, we demonstrate the power of multi-parametric dataset to describe ageing, to quantify health and to predict specific health risks.

systems biology↗