A neurotransmitter atlas ofC. elegansmales and hermaphrodites DOI Creative Commons
Chen Wang,

Berta Vidal,

Surojit Sural

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 25, 2023

ABSTRACT 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 C. 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 (glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, octopamine) both hermaphrodite male. Our reveals novel sites systems within glia, as well non-neural cells. The resulting atlas defines be exclusively neuropeptidergic, substantially expands repertoire capable co-transmitting multiple neurotransmitters, identifies uptake monoaminergic neurotransmitters. Furthermore, we observed unusual co-expression synthesis genes, suggesting existence transmitters. results what constitutes most extensive whole-animal-wide map usage date, paving way better communication specification .

Language: Английский

The neuropeptidergic connectome of C. elegans DOI Creative Commons
Lidia Ripoll-Sánchez, Jan Watteyne, HaoSheng Sun

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(22), P. 3570 - 3589.e5

Published: Nov. 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.

Language: Английский

Citations

92
Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification DOI Creative Commons
Molly B. Reilly,

Tessa Tekieli,

Cyril Cros

et al.

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(9), P. e1010372 - e1010372

Published: Sept. 30, 2022

Homeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In nematode Caenorhabditis elegans, each individual neuron class is defined by expression unique combinations homeobox genes, prompting question whether indeed requires a gene for its proper identity specification. We present here progress addressing this extending previous mutant analysis family members and describing multiple examples different parts C. elegans system. To probe function, we make use number reporter tools, including novel multicolor transgene, NeuroPAL, permits simultaneous monitoring execution differentiation programs throughout entire Using these add characterization identifying defects 14 24 distinct classes that mostly unrelated location, lineage history. 12 had no ascribed them before, while other classes, extend combinatorial code transcription factors required specifying terminal programs. Furthermore, demonstrate particular lineage, homeotic transformations occur upon loss show result changes codes. Combining with past analyses, 113 118 now known require Such broad deployment indicates specification may be an ancestral feature systems.

Language: Английский

Citations

39
Neuronal contact predicts connectivity in the C. elegans brain DOI Creative Commons
Steven J. Cook, Cristine A. Kalinski, Oliver Hobert

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(11), P. 2315 - 2320.e2

Published: May 26, 2023

Axons must project to particular brain regions, contact adjacent neurons, and choose appropriate synaptic targets form a nervous system. Multiple mechanisms have been proposed explain partnership choice. In "lock-and-key" mechanism, first by Sperry's chemoaffinity model,1 neuron selectively chooses partner among several different, target cells, based on specific molecular recognition code.2 Alternatively, Peters' rule posits that neurons indiscriminately connections with other types in their proximity; hence, neighborhood choice, determined initial neuronal process outgrowth position, is the main predictor of connectivity.3,4 However, whether plays an important role wiring remains unresolved.5 To assess nanoscale relationship between adjacency connectivity, we evaluate expansive set C. elegans connectomes. We find specificity can be accurately modeled as mediated neurite threshold strata, offering strong support for organizational principle wiring.

Language: Английский

Citations

25
Identification of multiple transcription factor genes potentially involved in the development of electrosensory versus mechanosensory lateral line organs DOI Creative Commons
Martin Minařík, Melinda S. Modrell, J. Andrew Gillis

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: March 18, 2024

In electroreceptive jawed vertebrates, embryonic lateral line placodes give rise to electrosensory ampullary organs as well mechanosensory neuromasts. Previous reports of shared gene expression suggest that conserved mechanisms underlie electroreceptor and hair cell development electroreceptors evolved a transcriptionally related “sister type” cells. We previously identified only one transcription factor gene, Neurod4 , organ-restricted in the developing system chondrostean ray-finned fish, Mississippi paddlefish ( Polyodon spathula ). The other 16 genes we validated were expressed both Here, used our published organ-enriched gene-set (arising from differential bulk RNA-seq late-larval paddlefish), together with candidate approach, identify 25 more experimentally tractable chondrostean, sterlet Acipenser ruthenus small sturgeon), and/or paddlefish. Thirteen are neuromasts, consistent conservation molecular mechanisms. Seven electrosensory-restricted on head Irx5 Irx3 Insm1 Sp5 Satb2 Mafa Rorc ), five first-reported mechanosensory-restricted Foxg1 Sox8 Isl1 Hmx2 Rorb However, reported, is neuromasts catshark Scyliorhinus canicula suggesting existence lineage-specific differences between cartilaginous fishes. Overall, results support hypothesis develop via largely transcriptional mechanisms, multiple factors potentially involved formation versus organs.

Language: Английский

Citations

6
A neurotransmitter atlas of C. elegans males and hermaphrodites DOI Creative Commons
Chen Wang,

Berta Vidal,

Surojit Sural

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: March 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 .

Language: Английский

Citations

6
A neurotransmitter atlas of C. elegans males and hermaphrodites DOI Creative Commons
Chen Wang,

Berta Vidal,

Surojit Sural

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Oct. 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 .

Language: Английский

Citations

5
Spatiotemporal analysis of mRNA-protein relationships enhances transcriptome-based developmental inference DOI Creative Commons

Duchangjiang Fan,

Yulin Cong, Jinyi Liu

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113928 - 113928

Published: March 1, 2024

Elucidating the complex relationships between mRNA and protein expression at high spatiotemporal resolution is critical for unraveling multilevel gene regulation enhancing mRNA-based developmental analyses. In this study, we conduct a single-cell analysis of transcription factors throughout C. elegans embryogenesis. Initially, cellular co-presence low, increasing to medium-high level (73%) upon factoring in delayed synthesis long-term persistence. These substantially affect mRNA-protein concordance, leading potential inaccuracies mRNA-reliant detection specificity characterization. Building on learned relationship, infer presence from demonstrate its utility identifying tissue-specific genes elucidating cells. This approach facilitates role sptf-1/SP7 neuronal lineage development. Collectively, study provides insights into dynamics during rapid embryogenesis approaches improving efficacy transcriptome-based

Language: Английский

Citations

4
Neurogenesis in Caenorhabditis elegans DOI Creative Commons
Richard J. Poole, Nuria Flames, Luisa Cochella

et al.

Genetics, Journal Year: 2024, Volume and Issue: 228(2)

Published: Aug. 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.

Language: Английский

Citations

4
An enteric neuron-expressed variant ionotropic receptor detects ingested salts to regulate salt stress resistance DOI
Jihye Yeon,

Laurie Chen,

Nikhila Krishnan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

ABSTRACT The detection of internal chemicals by interoceptive chemosensory pathways is critical for regulating metabolism and physiology. molecular identities interoceptors, the functional consequences chemosensation specific neurons remain to be fully described. C. elegans pharyngeal neuronal network anatomically functionally homologous mammalian enteric nervous system. Here, we show that I3 neuron responds cations via an I3-specific variant ionotropic receptor (IR) regulate salt stress tolerance. GLR-9 IR, located at gut lumen-exposed sensory end I3, necessary sufficient sensation, establishing a function IRs beyond insects. Salt protects specifically against high stress, as glr-9 mutants reduced tolerance hypertonic but not sugar solutions, with or without prior acclimation. While cholinergic signaling from promotes acute peptidergic during acclimation essential resistance subsequent challenge. Transcriptomic analyses regulates in part expression osmotic response genes distal tissues. Our results describe mechanisms which mediated defined physiological homeostasis abiotic stress.

Language: Английский

Citations

0
FGF-dependent, polarized SOS activity orchestrates directed migration ofC. elegansmuscle progenitors independently of canonical effectors in vivo DOI Creative Commons
Theresa V Gibney, Jacob I. Mardick, Neal R. Rasmussen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Summary Directed cell migration is essential for animal development, tissue maintenance, regeneration, and disease states. Cells often migrate towards, or away from, sources of secreted signaling proteins that impart spatial information. How migrating cells interpret extracellular signals to orient navigate within living animals a fundamental question in biology. Receptor Tyrosine Kinase (RTK) plays critical roles migration, aberrant RTK pathway activity key driver multiple types cancers. Yet, how RTKs control remains unclear, part due essential, pleiotropic development. To elucidate controls vivo , we used C. elegans muscle progenitor as tractable system dissect temporal requirements signal transduction cytoskeletal regulatory proteins. Cell type-specific depletion endogenously tagged revealed homologs FGFR, GRB2, SOS, Ras independent their canonical ERK, PI3K, AKT, mTOR, PLCγ effectors. Instead, found FGF-dependent, polarized SOS-1 orients towards an FGF source, mislocalizing SOS severely disrupts ERK. gain-of-function experiments demonstrated activated Ras/LET-60 acts permissively this context, intragenic revertant identified screen suppressors Ras/let-60 progenitors can be genetically uncoupled from other Ras-dependent developmental processes. Our findings provide novel mechanism RTK-directed highlight the importance approaches mechanisms physiologically relevant contexts. work also outlines comprehensive framework investigating RTK-dependent processes multicellular organism introduces versatile genetic toolkit dissecting dynamics homeostasis,

Language: Английский

Citations

0