Abstract
Proprioceptive feedback mainly derives from groups Ia and II muscle spindle (MS) afferents and group Ib Golgi tendon organ (GTO) afferents, but the molecular correlates of these three afferent subtypes remain unknown. We performed single cell RNA sequencing of genetically identified adult proprioceptors and uncovered five molecularly distinct neuronal clusters. Validation of cluster-specific transcripts in dorsal root ganglia and skeletal muscle demonstrates that two of these clusters correspond to group Ia MS afferents and group Ib GTO afferent proprioceptors, respectively, and suggest that the remaining clusters could represent group II MS afferents. Lineage analysis between proprioceptor transcriptomes at different developmental stages provides evidence that proprioceptor subtype identities emerge late in development. Together, our data provide comprehensive molecular signatures for groups Ia and II MS afferents and group Ib GTO afferents, enabling genetic interrogation of the role of individual proprioceptor subtypes in regulating motor output.
Highlights
Proprioceptive feedback mainly derives from groups Ia and II muscle spindle (MS) afferents and group Ib Golgi tendon organ (GTO) afferents, but the molecular correlates of these three afferent subtypes remain unknown
Proprioceptive muscle feedback is relayed though muscle spindle and GTO sensory afferents, yet little is known about the diversity among these afferents beyond the broad distinctions between their receptor and central targets
While previous transcriptome studies have revealed general proprioceptor markers based on comparisons to other somatosensory modalities, our unbiased analyses selectively focused on proprioceptive muscle afferents
Summary
Proprioceptive feedback mainly derives from groups Ia and II muscle spindle (MS) afferents and group Ib Golgi tendon organ (GTO) afferents, but the molecular correlates of these three afferent subtypes remain unknown. Many decades of study of the intramuscular sense organs and their afferent innervation have led to predictions on how proprioceptive feedback integrates with other sensory modalities to influence central motor circuits and calibrate motor output, yet most of these inferences await further corroboration in behaving animals[4,5,6] At present, such studies remain challenging due to the lack of genetic access to individual proprioceptor subtypes. Muscle spindle (MS) mechanoreceptors are considered the main drivers for the sense of limb position and movement (kinesthetic sense)[8,9] They are embedded within the belly of skeletal muscles and consist of encapsulated intrafusal muscle fibers that are typically innervated by one primary (group Ia) and several secondary (group II) proprioceptive sensory neurons (pSNs) (Fig. 1a)[7,10]. To what extent these properties are intrinsic to the neurons or to their association with different intrafusal muscle fibers remains poorly understood
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