Apr 5, 2020

Molecular development of muscle spindle and Golgi tendon organ sensory afferents revealed by single proprioceptor transcriptome analysis

BioRxiv : the Preprint Server for Biology
K. M. OliverJoriene C de Nooij

Abstract

Anatomical and physiological analyses have long revealed differences between proprioceptive groups Ia, II, and Ib sensory neurons, yet the molecular correlates of these three muscle afferent subtypes remain unknown. We performed single cell RNA sequencing of genetically identified adult proprioceptors and, using unbiased bioinformatics approaches, detected five molecularly distinct neuronal clusters. Validation of cluster-specific transcripts in dorsal root ganglia (DRG) and skeletal muscle provides evidence these clusters correspond to functionally distinct muscle spindle (MS) or Golgi tendon organ (GTO) afferent proprioceptors. Remarkably, while we uncovered just one type of GTO afferents, four of the five clusters represent MS afferents, thus demonstrating a previously unappreciated diversity among these muscle proprioceptors. In vitro electrophysiological recordings reveal just two broadly distinct proprioceptor types, and suggest that the refinement of functional subtype diversity may occur along multiple axes of maturation. Lineage analysis between proprioceptor transcriptomes at different developmental stages show little or no correlation for transcripts that define adult MS or GTO afferents, supporting the idea that pro...Continue Reading

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