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Proprioception is governed by highly diverse and versatile sensory neuron types

ABSTRACT: Proprioception is governed by highly diverse and versatile sensory neuron types

PROVIDER: PRJNA657004 | ENA |

REPOSITORIES: ENA

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Proprioception is governed by highly diverse and versatile sensory neuron types

Project description:Proprioceptive neurons (PNs) are essential for the proper execution of all our movements by providing muscle sensory feedback to the central motor network. Here, using deep single cell RNAseq of adult PNs coupled with advanced virus- and genetic tracings, we have molecularly identified the 3 main types of PNs (Ia, Ib and II) and unexpectedly found that they segregate into 8 subgroups. Our data further reveal a highly sophisticated organization of PNs into discrete sensory input channels with distinct spatial distribution, innervation patterns and molecular profiles, that together contribute to the sensory monitoring of complex motor behavior. Moreover, while Ib- and II-PN subtypes are specified around birth, Ia-PN subtypes diversify later along with increased motor activity and show versatility in the adult following exercise training, suggesting adaptive proprioceptive function.

2020-12-25 | GSE156180 | GEO

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Evolutionary decoupling of somatosensory circuit architecture and sensory neuron identity

Project description:The extent to which conserved neural circuit architectures depend on shared molecular specification programs remains unclear. Here, we address this problem in the vertebrate somatosensory system using the little skate (Leucoraja erinacea), an early-diverging vertebrate that retains ancestral features of both finned and limb-based body plans. Combining molecular profiling, spatial transcriptomics, and embryological manipulations, we show that core features of somatosensory circuit organization—including laminar organization of the dorsal spinal cord and modality-specific targeting of sensory afferents—are deeply conserved. In contrast, the molecular programs that define sensory neuron subtypes are extensively reconfigured, including divergent neurotrophin receptor and transcription factor codes. We demonstrate that target-derived cues regulate molecular programs and are required for sensory neuron differentiation and circuit assembly. Together, these findings support a model in which conserved circuit architectures provide a stable scaffold that leverages flexible molecular programs to enable the evolutionary diversification of sensory systems.

2026-07-28 | GSE334356 | GEO

Sensory neuron dysfunction in dorsal root ganglia during disease onset in the SOD1G93A mouse model for ALS

Project description:Amyotrophic lateral sclerosis (ALS) is primarily characterized by motor neuron degeneration, but accumulating evidence suggests that sensory neurons are also affected. To investigate early sensory neuron dysfunction in ALS, we performed bulk RNA sequencing of dorsal root ganglia (DRG) isolated from SOD1-G93A transgenic mice and wild-type controls at disease onset. This dataset provides transcriptomic profiles that reveal molecular alterations associated with ALS-related sensory neuron pathology.

2026-03-25 | GSE318631 | GEO

Evolutionary decoupling of somatosensory circuit architecture and sensory neuron identity

Project description:Deeply conserved neural circuit architectures often depend on shared fate specification programs. The extent to which circuit evolution relies on the diversification of neuronal identities versus rewiring of existing populations remains poorly defined. We addressed this problem by examining the somatosensory system of the skate Leucoraja erinacea, leveraging its 420-million-year separation from mammals. We find that core somatosensory circuit features - including layering of the dorsal spinal cord and modality-specific targeting of sensory afferents - are deeply conserved, thus defining an ancestral vertebrate organization. Unexpectedly, the molecular programs specifying sensory subtypes diverge extensively from those in mammals. Although sensory neuron identity and spinal connectivity rely on target-derived cues, skates employ distinct and neurotrophin receptor and transcription factor identity codes. We propose that ancient spinal circuit organization functions as a scaffold that preserves system integrity while permitting diversification of sensory neuron regulatory programs, suggesting a general strategy for somatosensory circuit evolution.

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Project description:Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of cancer treatment, yet the lack of predictive human models has hindered therapeutic progress. We have established a scalable model of paclitaxel-induced axon degeneration and neurotoxicity in iPSC-derived sensory neurons, suitable for high-throughput discovery of neuroprotective compounds. Using this platform, we screened 192 kinase inhibitors and identified 19 hits that commonly inhibited three STE20 kinases - MAP4K4, MINK1, and TNIK. Genetic knockdown revealed that multi-kinase inhibition of STE20 kinases is required for neuroprotection against paclitaxel. Moreover, selective pharmacological inhibition of STE20 kinases rescued paclitaxel-induced axon degeneration in iPSC-derived sensory neurons and primary human DRG, as well as preserved intraepidermal nerve fiber density in a mouse model of CIPN. These results establish a translational human sensory neuron platform for target and drug discovery in CIPN.

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