System-wide mapping of peptide-GPCR interactions in C. elegans

Cell Reports, Год журнала: 2023, Номер 42(9), С. 113058 - 113058

Опубликована: Авг. 31, 2023

Neuropeptides and peptide hormones are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of peptidergic network roles many peptides remain elusive, as our insight into peptide-receptor interactions is limited GPCRs still orphan receptors. Here we report genome-wide peptide-GPCR interaction map in Caenorhabditis elegans. By reverse pharmacology screening over 55,384 possible interactions, identify 461 cognate couples uncover with specific complex combinatorial encoded across within single genes. These provide insights functions evolution. Combining dataset phylogenetic analysis supports co-evolution conservation at least 14 bilaterian systems C. This resource lays foundation for system-wide network.

Язык: Английский

---

A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes

Cell Reports, Год журнала: 2024, Номер 43(3), С. 113857 - 113857

Опубликована: Фев. 29, 2024

Motor neurons (MNs) constitute an ancient cell type targeted by multiple adult-onset diseases. It is therefore important to define the molecular makeup of adult MNs in animal models and extract organizing principles. Here, we generate a comprehensive atlas Caenorhabditis elegans searchable database. Single-cell RNA sequencing 13,200 cells reveals that ventral nerve cord cluster into 29 molecularly distinct subclasses. Extending C. Neuronal Gene Expression Map Network (CeNGEN) findings, all MN subclasses are delineated expression codes either neuropeptide or transcription factor gene families. Strikingly, combinatorial homeodomain genes succinctly delineate diversity both mice. Further, defined display patterns connectivity. Hence, our study couples connectivity map motor circuit with its constituent uncovers principles conserved diversity.

Язык: Английский

---

Antagonism between neuropeptides and monoamines in a distributed circuit for pathogen avoidance

Cell Reports, Год журнала: 2024, Номер 43(4), С. 114042 - 114042

Опубликована: Апрель 1, 2024

Pathogenic infection elicits behaviors that promote recovery and survival of the host. After exposure to pathogenic bacterium Pseudomonas aeruginosa PA14, nematode Caenorhabditis elegans modifies its sensory preferences avoid pathogen. Here, we identify antagonistic neuromodulators shape this acquired avoidance behavior. Using an unbiased cell-directed neuropeptide screen, show AVK neurons upregulate release RF/RYamide FLP-1 neuropeptides during drive pathogen avoidance. Manipulations increase or decrease activity accelerate delay avoidance, respectively, implicating in dynamics through G protein-coupled receptor DMSR-7, as well other receptors. DMSR-7 turn acts multiple neurons, including tyraminergic/octopaminergic receive convergent signals from cytokine DAF-7/transforming growth factor β. Neuromodulators mechanisms targets, agreement with distributed neuromodulatory connectome C. elegans.

Язык: Английский

---

Understanding neural circuit function through synaptic engineering

Nature reviews. Neuroscience, Год журнала: 2024, Номер 25(2), С. 131 - 139

Опубликована: Янв. 3, 2024

Язык: Английский

---

Synaptic connectome of the Drosophila circadian clock

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 5, 2024

Abstract The circadian clock and its output pathways play a pivotal role in optimizing daily processes. To obtain insights into how diverse rhythmic physiology behaviors are orchestrated, we have generated comprehensive connectivity map of an animal using the Drosophila FlyWire brain connectome. Intriguingly, identified additional dorsal neurons, thus showing that network contains ~240 instead 150 neurons. We revealed extensive contralateral synaptic within discovered novel indirect light input to also elucidated via which modulates descending neurons known regulate feeding reproductive behaviors. Interestingly, observed sparse monosynaptic between downstream higher-order centers neurosecretory cells behavior physiology. Therefore, integrated single-cell transcriptomics receptor mapping decipher putative paracrine peptidergic signaling by Our analyses neuropeptides expressed suggest significantly enriches interconnectivity network.

Язык: Английский

---

Applications of machine learning and deep learning in medical diagnosis

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 47 - 82

Опубликована: Янв. 1, 2025

Язык: Английский

---

Utilization of Artificial Intelligence Coupled with a High-Throughput, High-Content Platform in the Exploration of Neurodevelopmental Toxicity of Individual and Combined PFAS

Journal of Xenobiotics, Год журнала: 2025, Номер 15(1), С. 24 - 24

Опубликована: Фев. 2, 2025

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various products, such as firefighting foams non-stick cookware, due to their resistance heat degradation. However, these same properties make them persistent the environment human body, raising public health concerns. This study selected eleven PFAS commonly found drinking water exposed Caenorhabditis elegans concentrations ranging from 0.1 200 µM assess neurodevelopmental toxicity using a high-throughput, high-content screening (HTS) platform coupled with artificial intelligence for image analysis. Our findings showed that 6:2 FTS, HFPO-DA, PFBA, PFBS, PFHxA, PFOS inhibited dopaminergic neuron activity, fluorescence intensity reductions observed across 100 µM. PFBS also disrupted synaptic transmission, causing reduced motility increased paralysis aldicarb-induced assays, most pronounced effects at higher concentrations. These impairments both activity function led behavioral deficits. Notably, was one of toxic PFAS, affecting multiple endpoints. results emphasize developmental risks exposure, highlighting impact individual compounds mixtures on neurodevelopment. knowledge is essential assessing PFAS-related informing mitigation strategies.

Язык: Английский

---

Synaptic connectome of theDrosophilacircadian clock

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 13, 2023

The circadian clock and its output pathways play a pivotal role in optimizing daily processes. To obtain novel insights into how diverse rhythmic physiology behaviors are orchestrated, we have generated the first comprehensive connectivity map of an animal using Drosophila FlyWire brain connectome. Intriguingly, identified additional dorsal neurons, thus showing that network contains ∼240 instead 150 neurons. We also revealed extensive contralateral synaptic within discovered indirect light input to Interestingly, observed sparse monosynaptic between neurons down-stream higher-order centers neurosecretory cells known regulate behavior physiology. Therefore, integrated single-cell transcriptomics receptor mapping decipher putative paracrine peptidergic signaling by Our analyses neuropeptides expressed suggest significantly enriches interconnectivity network.

Язык: Английский

---

A single neuron in C. elegans orchestrates multiple motor outputs through parallel modes of transmission

Current Biology, Год журнала: 2023, Номер 33(20), С. 4430 - 4445.e6

Опубликована: Сен. 27, 2023

Animals generate a wide range of highly coordinated motor outputs, which allows them to execute purposeful behaviors. Individual neurons in the circuits that behaviors have remarkable capacity for flexibility as they exhibit multiple axonal projections, transmitter systems, and modes neural activity. How these multi-functional properties enable generation adaptive remains unknown. Here, we show HSN neuron C. elegans evokes programs over different timescales suite behavioral changes during egg laying. Using activity perturbations vivo calcium imaging, acutely increases laying locomotion while also biasing animals toward low-speed dwelling behavior minutes. The acute effects on high-speed are mediated by separate sets transmitters compartments. long-lasting part release serotonin, is taken up re-released NSM, another serotonergic class directly dwelling. Our results how single allow it induce reveal can borrow serotonin from one control behavior.

Язык: Английский

---

Evolutionary conserved peptide and glycoprotein hormone-like neuroendocrine systems in C. elegans

Molecular and Cellular Endocrinology, Год журнала: 2024, Номер 584, С. 112162 - 112162

Опубликована: Янв. 28, 2024

Peptides and protein hormones form the largest group of secreted signals that mediate intercellular communication are central regulators physiology behavior in all animals. Phylogenetic analyses biochemical identifications peptide-receptor systems reveal a broad evolutionary conservation these signaling at molecular level. Substantial progress has been made recent years on characterizing physiological putative ancestral roles many peptide through comparative studies invertebrate models. Several peptides not only molecularly conserved but also have across animal phyla. Here, we focus functional insights gained nematode Caenorhabditis elegans that, with its compact well-described nervous system, provides powerful model to dissect neuroendocrine networks involved control behavior. We summarize discoveries knowledge functions hormone C. elegans.

Язык: Английский

---