Neurogenesis in Caenorhabditis elegans

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

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Epithelial UNC-23 limits mechanical stress to maintain glia-neuron architecture in C. elegans

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(13), P. 1668 - 1688.e7

Published: April 25, 2024

For an organ to maintain correct architecture and function, its diverse cellular components must coordinate their size shape. Although cell-intrinsic mechanisms driving homotypic cell-cell coordination are known, it is unclear how cell shape regulated across heterotypic cells. We find that epithelial cells the of neighboring sense-organ glia-neuron units in adult Caenorhabditis elegans (C. elegans). Hsp co-chaperone UNC-23/BAG2 prevents from deforming, loss causes head epithelia stretch aberrantly during animal movement. In glia, amphid sheath (AMsh), this progressive fibroblast growth factor receptor (FGFR)-dependent disruption glial apical cytoskeleton. Resultant alteration concomitant change glia-associated neuron endings. Epithelial UNC-23 maintenance specific both spatially, within a defined anatomical zone, temporally, developmentally critical period. As all molecular uncovered broadly conserved central peripheral nervous systems, we posit may similarly regulate cross-species.

Language: Английский

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Antagonist actions of CMK-1/CaMKI and TAX-6/Calcineurin along the C. elegans thermal avoidance circuit orchestrate nociceptive habituation

Published: Jan. 28, 2025

Habituation is a conserved physiological phenomenon, during which responses decrease following repeated exposure to innocuous or noxious stimuli. Impaired nociceptive habituation associated with several pain conditions in human, but the underpinning molecular mechanisms are only partially understood. In nematode Caenorhabditis elegans , thermo-nociceptive was previously shown be regulated by Ca 2+ /Calmodulin-dependent protein kinase 1 (named CMK-1), its downstream effectors were unknown. Here, using vitro assays coupled mass-spectrometry-based phosphoproteomics, we empirically identified hundreds of CMK-1 phospho-substrates. Among them, found that can phosphorylate calcineurin A (CnA) TAX-6 highly regulatory domain. Combined genetic and pharmacological manipulations revealed network antagonistic actions between pathways regulation responsiveness naïve worms their heat We further highlighted multiple places action two signaling subset thermosensory neurons interneurons mediating avoidance behaviors. As whole, our study has (i) substrate candidates, will fuel research on intracellular actuation CMK-1-dependent signaling, (ii) complex set interactions operating at distributed loci within sensory-behavior circuit, acting adjust baseline thermo-nociception regulate habituation.

Language: Английский

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Antagonist actions of CMK-1/CaMKI and TAX-6/Calcineurin along the C. elegans thermal avoidance circuit orchestrate nociceptive habituation

Published: Jan. 28, 2025

Habituation is a conserved physiological phenomenon, during which responses decrease following repeated exposure to innocuous or noxious stimuli. Impaired nociceptive habituation associated with several pain conditions in human, but the underpinning molecular mechanisms are only partially understood. In nematode Caenorhabditis elegans , thermo-nociceptive was previously shown be regulated by Ca 2+ /Calmodulin-dependent protein kinase 1 (named CMK-1), its downstream effectors were unknown. Here, using vitro assays coupled mass-spectrometry-based phosphoproteomics, we empirically identified hundreds of CMK-1 phospho-substrates. Among them, found that can phosphorylate calcineurin A (CnA) TAX-6 highly regulatory domain. Combined genetic and pharmacological manipulations revealed network antagonistic actions between pathways regulation responsiveness naïve worms their heat We further highlighted multiple places action two signaling subset thermosensory neurons interneurons mediating avoidance behaviors. As whole, our study has (i) substrate candidates, will fuel research on intracellular actuation CMK-1-dependent signaling, (ii) complex set interactions operating at distributed loci within sensory-behavior circuit, acting adjust baseline thermo-nociception regulate habituation.

Language: Английский

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Antagonist actions of CMK-1/CaMKI and TAX-6/Calcineurin along the C. elegans thermal avoidance circuit orchestrate adaptation of nociceptive response to repeated stimuli

Published: April 16, 2025

Response decrease following repeated exposure to innocuous or noxious stimuli is a conserved adaptation phenomenon often referred as habituation. Impaired nociceptive habituation associated with several pain conditions in human, but the underpinning molecular mechanisms are only partially understood. In nematode Caenorhabditis elegans , thermo-nociceptive was previously shown be regulated by Ca 2+ /Calmodulin-dependent protein kinase 1 (named CMK-1), its downstream effectors were unknown. Here, using vitro assays coupled mass-spectrometry-based phosphoproteomics, we empirically identified hundreds of CMK-1 phospho-substrates. Among them, found that can phosphorylate calcineurin A (CnA) TAX-6 highly regulatory domain, which led us hypothesize TAX-6/CnA might mediator signaling control adaptation. Combined genetic and pharmacological manipulations revealed network antagonistic actions between pathways regulation responsiveness naïve worms response heat stimuli. However, results cell-specific rescue gain-of-function experiments suggested acts AFD ASER thermosensory neurons FLP neuron set interneurons regulate avoidance behaviors. Because act non-overlapping cell types, phosphorylation event not relevant for this phenotype complex interaction two rather originate from their action separate parts nervous system. As whole, our study has (i) substrate candidates, will fuel further research on intracellular actuation CMK-1-dependent various processes, (ii) interactions operating at distributed loci within sensory-behavior circuit, acting adjust baseline thermo-nociception

Language: Английский

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Mapping and decoding neuropeptide signaling networks in nervous system function

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 103027 - 103027

Published: April 21, 2025

Neuropeptides are widespread signaling molecules that central to brain function in all animals. Recent advances profiling their expression across neural circuits, conjunction with detailed biochemical characterization of interactions receptors, have made it feasible build brain-wide maps neuropeptide signaling. Here, we discuss how recent reconstructions networks, from mammalian regions nervous system-wide C. elegans, reveal conserved organizational features neuropeptidergic networks. Furthermore, review technical breakthroughs vivo sensors for peptide release, receptor binding, and intracellular bring a mechanistic understanding networks within experimental reach. Finally, describe the architecture can change throughout evolution or even lifetime individuals, which highlights complexities must be considered understand these modulate circuit activity behavior different contexts.

Language: Английский

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Chromatin regulation of neuronal activity-dependent gene programs in circuit formation and plasticity

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 103024 - 103024

Published: April 21, 2025

Neuronal activity-dependent transcription is crucial for the development and plasticity of neuronal circuits. At chromatin level, induction activity-regulated genes orchestrated through various mechanisms, including deposition histone modifications at regulatory elements, binding transcriptional activators repressors, remodeling, control 3D genome architecture. Here, we review our current understanding how mechanisms regulate temporally distinct waves following stimulation allow neurons to mount cell type-specific stimulus-specific responses. We also highlight a specific epigenetic mechanism in developing that maintains immediate early (IEGs) an inactive though poised state, while simultaneously preparing them rapid activation response sensory stimulation. discuss regulation play role controlling gene expression, enabling implementation precise expression programs during different stages neural circuit plasticity.

Language: Английский

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Antagonist actions of CMK-1/CaMKI and TAX-6/calcineurin along the C. elegans thermal avoidance circuit orchestrate adaptation of nociceptive response to repeated stimuli

eLife, Journal Year: 2025, Volume and Issue: 14

Published: April 30, 2025

Thermal nociception in Caenorhabditis elegans is regulated by the Ca² + /calmodulin-dependent protein kinase CMK-1, but its downstream effectors have remained unclear. Here, we combined vitro assays with mass-spectrometry-based phosphoproteomics to identify hundreds of CMK-1 substrates, including calcineurin A subunit TAX-6, phosphorylated within conserved regulatory domain. Genetic and pharmacological analyses reveal multiple antagonistic interactions between signaling modulating both naive thermal responsiveness adaptation repeated noxious stimuli. Cell-specific manipulations indicate that acts AFD ASER thermo-sensory neurons, while TAX-6 functions FLP neurons interneurons. Since act distinct cell types, phosphorylation observed might not directly underlie behavioral phenotype. Instead, opposing effects seem arise from their distributed roles sensory circuit. Overall, our study provides (1) a resource candidate targets for further dissecting CaM (2) evidence previously unrecognized, circuit-level antagonism pathways. These findings highlight complex interplay modules modulate adaptation, offering new insights into potentially mechanisms shape nociceptive plasticity pain (de)sensitization more nervous systems.

Language: Английский

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Activity-dependent development of the body’s touch receptors

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

We report a role for activity in the development of primary sensory neurons that detect touch. Genetic deletion Piezo2, principal mechanosensitive ion channel somatosensory neurons, caused profound changes formation mechanosensory end-organ structures. Peripheral-nervous-system-specific voltage-gated sodium Nav1.6 (Scn8a), which resulted altered electrophysiological responses to mechanical stimuli, also disrupted neuron morphologies, supporting neuronal formation. Single-cell RNA sequencing Piezo2 mutants revealed gene expression activated by light forces, whereas other classes were minimally affected, and genetic Piezo2-dependent genes partially reproduced defects structures observed mutants. These findings indicate mechanically evoked acts early life shape maturation end-organs underlie our sense gentle

Language: Английский

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Activity-dependent development of the body’s touch receptors

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

Published: Sept. 24, 2023

We report a role for activity in the development of primary sensory neurons that detect touch. Genetic deletion Piezo2, principal mechanosensitive ion channel somatosensory neurons, caused profound changes formation mechanosensory end organ structures and altered neuron central targeting. Single cell RNA sequencing

Language: Английский

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