The neuropeptidergic connectome of C. elegans

Neuron, Год журнала: 2023, Номер 111(22), С. 3570 - 3589.e5

Опубликована: Ноя. 1, 2023

Efforts are ongoing to map synaptic wiring diagrams, or connectomes, understand the neural basis of brain function. However, chemical synapses represent only one type functionally important neuronal connection; in particular, extrasynaptic, "wireless" signaling by neuropeptides is widespread and plays essential roles all nervous systems. By integrating single-cell anatomical gene-expression datasets with biochemical analysis receptor-ligand interactions, we have generated a draft connectome neuropeptide C. elegans system. This network characterized high connection density, extended cascades, autocrine foci, decentralized topology, large, highly interconnected core containing three constituent communities sharing similar patterns input connectivity. Intriguingly, several key hubs little-studied neurons that appear specialized for peptidergic neuromodulation. We anticipate neuropeptidergic will serve as prototype how networks neuromodulatory organized.

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

---

Caenorhabditis elegans sine oculis/SIX-type homeobox genes act as homeotic switches to define neuronal subtype identities

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(37)

Опубликована: Сен. 6, 2022

The classification of neurons into distinct types reveals hierarchical taxonomic relationships that reflect the extent similarity between neuronal cell types. At base such taxonomies are cells very similar to one another but differ in a small number reproducible and select features. How members neuron class share many features instructed diversify subclasses? We show here six

Язык: Английский

---

A neurotransmitter atlas of C. elegans males and hermaphrodites

eLife, Год журнала: 2024, Номер 13

Опубликована: Март 20, 2024

Mapping neurotransmitter identities to neurons is key understanding information flow in a nervous system. It also provides valuable entry points for studying the development and plasticity of neuronal identity features. In Caenorhabditis elegans system, have been largely assigned by expression pattern analysis pathway genes that encode biosynthetic enzymes or transporters. However, many these assignments relied on multicopy reporter transgenes may lack relevant cis -regulatory therefore not provide an accurate picture usage. We analyzed patterns 16 CRISPR/Cas9-engineered knock-in strains all main types neurotransmitters C. (glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, octopamine) both hermaphrodite male. Our reveals novel sites systems within glia, as well non-neural cells, most notably gonadal cells. The resulting atlas defines be exclusively neuropeptidergic, substantially expands repertoire capable co-transmitting multiple neurotransmitters, identifies monoaminergic uptake. Furthermore, we observed unusual co-expression synthesis genes, suggesting existence transmitters. results what constitutes extensive whole-animal-wide map usage date, paving way better communication specification .

Язык: Английский

---

A neurotransmitter atlas of C. elegans males and hermaphrodites

eLife, Год журнала: 2024, Номер 13

Опубликована: Окт. 18, 2024

Mapping neurotransmitter identities to neurons is key understanding information flow in a nervous system. It also provides valuable entry points for studying the development and plasticity of neuronal identity features. In Caenorhabditis elegans system, have been largely assigned by expression pattern analysis pathway genes that encode biosynthetic enzymes or transporters. However, many these assignments relied on multicopy reporter transgenes may lack relevant cis -regulatory therefore not provide an accurate picture usage. We analyzed patterns 16 CRISPR/Cas9-engineered knock-in strains all main types neurotransmitters C. (glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, octopamine) both hermaphrodite male. Our reveals novel sites systems within glia, as well non-neural cells, most notably gonadal cells. The resulting atlas defines be exclusively neuropeptidergic, substantially expands repertoire capable co-transmitting multiple neurotransmitters, identifies monoaminergic uptake. Furthermore, we observed unusual co-expression synthesis genes, suggesting existence transmitters. results what constitutes extensive whole-animal-wide map usage date, paving way better communication specification .

Язык: Английский

---

Neurogenesis in Caenorhabditis elegans

Genetics, Год журнала: 2024, Номер 228(2)

Опубликована: Авг. 21, 2024

Abstract Animals rely on their nervous systems to process sensory inputs, integrate these with internal signals, and produce behavioral outputs. This is enabled by the highly specialized morphologies functions of neurons. Neuronal cells share multiple structural physiological features, but they also come in a large diversity types or classes that give system its broad range plasticity. diversity, first recognized over century ago, spurred classification efforts based morphology, function, molecular criteria. Caenorhabditis elegans, precisely mapped at anatomical level, an extensive description most neurons, genetic amenability, has been prime model for understanding how neurons develop diversify mechanistic level. Here, we review gene regulatory mechanisms driving neurogenesis diversification neuron subclasses C. elegans. We discuss our current specification neuronal progenitors differentiation terms transcription factors involved ensuing changes expression chromatin landscape. The central theme emerged identity defined modules batteries are under control parallel yet interconnected mechanisms. focus how, achieve terminal identities, information along developmental lineages. Moreover, diversified postembryonically time-, sex-, activity-dependent manner. Finally, development can provide insights into evolution diversity.

Язык: Английский

---

Functional analysis of conserved C. elegans bHLH family members uncovers lifespan control by a peptidergic hub neuron

PLoS Biology, Год журнала: 2025, Номер 23(1), С. e3002979 - e3002979

Опубликована: Янв. 6, 2025

Throughout the animal kingdom, several members of basic helix-loop-helix (bHLH) family act as proneural genes during early steps nervous system development. Roles bHLH in specifying terminal differentiation postmitotic neurons have been less extensively studied. We analyze here function 5 Caenorhabditis elegans genes, falling into 3 phylogenetically conserved subfamilies, which are continuously expressed a very small number central system. show (a) that 2 orthologs vertebrate bHLHe22/e23 called hlh-17 and hlh-32, redundantly to specify identity single head interneuron class (AUA), well an individual motor neuron (VB2); (b) PTF1a ortholog hlh-13 acts selector control sole octopaminergic C. elegans, RIC; (c) NHLH1/2 hlh-15 controls peptidergic AVK class, known neuropeptidergic signaling hub animal. Strikingly, through null mutant analysis cell-specific rescue experiments, we find loss hlh-15/NHLH resulting abrogation neuropeptide secretion from these causes substantially extended lifespan animal, propose be akin hypothalamic vertebrates. Our functional reveals themes gene complementary earlier lineage specification roles other members. However, such late functions much more sparsely employed by transcription factor family, compared broadly homeodomain family.

Язык: Английский

---

Protocol to identify transcription factor target genes using TargetOrtho2

STAR Protocols, Год журнала: 2025, Номер 6(1), С. 103680 - 103680

Опубликована: Март 1, 2025

TargetOrtho2 uses transcription factor binding site information to predict targets in C. elegans, based on an silico phylogenetic footprinting approach. Here, we present a protocol identify target genes using new version of TargetOrtho2. We provide instructions for installing and its required suite programs, predicting genes, updating adding genomes

Язык: Английский

---

Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons

Опубликована: Апрель 11, 2025

Neuron-specific morphology and function are fundamentally tied to differences in gene expression across the nervous system. We previously generated a single cell RNA-seq (scRNA-Seq) dataset for every anatomical neuron class C. elegans hermaphrodite. Here we present complementary set of bulk samples 52 118 canonical classes . show that captures both lowly expressed noncoding RNAs not detected scRNA-Seq profile, but also includes false positives due contamination by other types. an analytical strategy integrates two datasets, preserving specificity data sensitivity RNA-Seq. this integrated enhances accuracy transcript detection differential analysis. In addition, RNA-Seq detects differentially non-coding types, including multiple families non-polyadenylated transcripts. propose our approach provides new interrogating bridging gap between methodologies transcriptomic studies. suggest these datasets advance goal delineating mechanisms define connectivity

Язык: Английский

---

Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons

Опубликована: Апрель 11, 2025

Neuron-specific morphology and function are fundamentally tied to differences in gene expression across the nervous system. We previously generated a single cell RNA-seq (scRNA-Seq) dataset for every anatomical neuron class C. elegans hermaphrodite. Here we present complementary set of bulk samples 52 118 canonical classes . show that captures both lowly expressed noncoding RNAs not detected scRNA-Seq profile, but also includes false positives due contamination by other types. an analytical strategy integrates two datasets, preserving specificity data sensitivity RNA-Seq. this integrated enhances accuracy transcript detection differential analysis. In addition, RNA-Seq detects differentially non-coding types, including multiple families non-polyadenylated transcripts. propose our approach provides new interrogating bridging gap between methodologies transcriptomic studies. suggest these datasets advance goal delineating mechanisms define connectivity

Язык: Английский

---