9/3/2023 0 Comments Blacksmith3d reset viewHowever, these datasets contain RNA transcripts expressed at the neuron cell body and nucleus, missing information on transcript expression at the terminal ends. These studies greatly advance our molecular understanding of proprioceptive and γ-motoneurons. Single-nucleus transcriptomic analysis of spinal cord motoneurons identified the transcriptional profile of γ-motoneurons ( Blum et al., 2021). Single-cell RNA analysis of dorsal root ganglion (DRG) proprioceptive neurons revealed their molecular diversity, subdividing these neurons to five to eight subgroups and identifying specific markers for the proprioceptive neurons composing muscle spindle ( Oliver et al., 2021 Wu et al., 2021). In recent years, attempts have been made to uncover the molecular composition of the spindle. These findings significantly increase the importance of the proprioceptive system and emphasize the need to understand the molecular mechanisms underlying its development and function. Previous work from our lab demonstrated that the proprioceptive system regulates several aspects of musculoskeletal development and function and that impaired proprioceptive signaling causes musculoskeletal pathology ( Assaraf et al., 2020 Blecher et al., 2017a Blecher et al., 2017b Bornstein et al., 2021). Nonetheless, the molecular events that regulate spindle development are largely unknown. This process is initiated when sensory neuron afferents contact immature myofibers and induce their differentiation ( Hippenmeyer et al., 2002). The development of the muscle spindle starts in utero and continues postnatally. This structure is partially isolated from its surroundings by a capsule rich in extracellular matrix (ECM) that is secreted by capsule cells ( Bewick and Banks, 2014 Kröger and Watkins, 2021). The spindle is composed of specialized muscle fibers, termed intrafusal fibers, which are innervated by proprioceptive sensory neurons at their central region and by γ-motoneurons at their polar ends. In mammalians, the muscle spindle is one of the main proprioceptive mechanosensory organs ( Proske and Gandevia, 2012). This information is then transferred to the central nervous system, where input from populations of proprioceptive neurons is integrated to generate the sense of position and movement of limb and trunk ( Kiehn, 2016 Proske and Gandevia, 2012 Sherrington, 1907). Proprioceptive information is produced by specialized mechanosensory organs located in muscles, tendons, and joints, which detect the stretch, tension, and force experienced by the muscles. The proprioceptive system is essential for controlling coordinated movement and posture. Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle isolated from the murine deep masseter muscle. Despite its importance, the molecular composition of the muscle spindle is largely unknown. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. The proprioceptive system is essential for the control of coordinated movement, posture, and skeletal integrity.
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