Molecular blueprints for spinal circuit modules controlling locomotor speed in zebrafish

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 27(1), P. 78 - 89

Published: Nov. 2, 2023

Abstract The flexibility of motor actions is ingrained in the diversity neurons and how they are organized into functional circuit modules, yet our knowledge molecular underpinning modularity remains limited. Here we use adult zebrafish to link motoneurons (MNs) rhythm-generating V2a interneurons (INs) with modular organization that responsible for changes locomotor speed. We show MNs INs reflects their segregation slow, intermediate or fast subtypes. Furthermore, reveal shared signatures between three speed modules. Overall, by characterizing relates function, connectivity behavior, study provides important insights not only mechanisms neuronal but also charting circuits general.

Language: Английский

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Single-cell analysis of Rohon-Beard neurons implicates Fgf signaling in axon maintenance and cell survival

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. e1600232024 - e1600232024

Published: Feb. 29, 2024

Peripheral sensory neurons are a critical part of the nervous system that transmit multitude stimuli to central system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory (RBs). RBs optically accessible amenable experimental manipulation, making them powerful for mechanistic investigation neurons. Previous studies provided evidence fall into multiple subclasses; however, number molecular make up these potential RB subtypes have not been well defined. Using single-cell RNA sequencing (scRNA-seq) approach, we demonstrate zebrafish unknown sex three, largely non-overlapping classes We also show molecularly distinct from trigeminal zebrafish. Cross-species transcriptional analysis indicates one subclass similar mammalian group A-fiber Another predicted sense modalities, including mechanical stimulation chemical irritants. leveraged our scRNA-seq data determine fibroblast growth factor (Fgf) pathway active RBs. Pharmacological genetic inhibition led defects axon maintenance cell death. Moreover, can be phenocopied treatment with dovitinib, an FDA-approved Fgf inhibitor common side effect peripheral neuropathy. Importantly, dovitinib-mediated loss suppressed Sarm1, positive regulator neuronal death axonal injury. This offers target future clinical intervention fight neurotoxic effects drug. SIGNIFICANCE STATEMENT Elucidating signaling pathways cellular mechanisms regulate neuron health understanding neuropathy etiologies exploring therapies. (RB) vivo model explore neurobiological such neuropathies. However, nature subpopulations fully explored. there three unique profiles. Furthermore, find has novel role survival Our work finds new axons provides first transcriptionally-based classification It sets stage how may involved

Language: Английский

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Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 25, 2023

Identification of the neuronal types that form specialized circuits controlling distinct behaviors has benefited greatly from simplicity offered by zebrafish. Electrophysiological studies have shown in addition to connectivity, understanding circuitry requires identification functional specializations among individual circuit components, such as those regulate levels transmitter release and excitability. In this study, we use single-cell RNA sequencing (scRNAseq) identify molecular bases for distinctions between motoneuron are causal their differential roles swimming. The primary motoneuron, particular, expresses high a unique combination voltage-dependent ion channel synaptic proteins termed 'cassettes.' promoting high-frequency firing action potentials augmented at neuromuscular junction, both contributing greater power generation. Our transcriptional profiling spinal neurons further assigns expression cassette specific interneuron also involved central high-speed swimming escape behaviors. analysis highlights utility scRNAseq characterization circuitry, providing gene resource studying cell type diversity.

Language: Английский

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Single-cell analysis of Rohon-Beard neurons implicates Fgf signaling in axon maintenance and cell survival

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

Published: Aug. 28, 2023

ABSTRACT Peripheral sensory neurons are a critical part of the nervous system that transmit multitude stimuli to central system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory (RBs). RBs optically accessible amenable experimental manipulation, making them powerful for mechanistic investigation neurons. Previous studies provided evidence fall into multiple subclasses; however, number molecular make up these potential RB subtypes have not been well defined. Using single-cell RNA sequencing (scRNA-seq) approach, we demonstrate zebrafish three, largely non-overlapping classes We also show molecularly distinct from trigeminal zebrafish. Cross-species transcriptional analysis indicates one subclass similar mammalian group A-fiber Another predicted sense modalities, including mechanical stimulation chemical irritants. leveraged our scRNA-seq data determine fibroblast growth factor (Fgf) pathway active RBs. Pharmacological genetic inhibition led defects axon maintenance cell death. Moreover, can be phenocopied treatment with dovitinib, an FDA-approved Fgf inhibitor common side effect peripheral neuropathy. Importantly, dovitinib-mediated loss suppressed Sarm1, positive regulator neuronal death axonal injury. This offers target future clinical intervention fight neurotoxic effects drug.

Language: Английский

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Zebrafish as a model to understand extraocular motor neuron diversity

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 90, P. 102964 - 102964

Published: Dec. 30, 2024

Language: Английский

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