The Proprioceptive System Masterminds Spinal Alignment: Insight into the Mechanism of Scoliosis

Ronen Blecher, Sharon Krief, Tal Galili, Inbal E. Biton, Tomer Stern, Eran Assaraf, Ditsa Levanon, Elena Appel, Yoram Anekstein, Gabriel Agar, Yoram Groner, Elazar Zelzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Maintaining posture requires tight regulation of the position and orientation of numerous spinal components. Yet, surprisingly little is known about this regulatory mechanism, whose failure may result in spinal deformity as in adolescent idiopathic scoliosis. Here, we use genetic mouse models to demonstrate the involvement of proprioception in regulating spine alignment. Null mutants for Runx3 transcription factor, which lack TrkC neurons connecting between proprioceptive mechanoreceptors and spinal cord, developed peripubertal scoliosis not preceded by vertebral dysplasia or muscle asymmetry. Deletion of Runx3 in the peripheral nervous system or specifically in peripheral sensory neurons, or of enhancer elements driving Runx3 expression in proprioceptive neurons, induced a similar phenotype. Egr3 knockout mice, lacking muscle spindles, but not Golgi tendon organs, displayed a less severe phenotype, suggesting that both receptor types may be required for this regulatory mechanism. These findings uncover a central role for the proprioceptive system in maintaining spinal alignment.

Original languageEnglish
Pages (from-to)388-399.e3
JournalDevelopmental Cell
Issue number4
StatePublished - 21 Aug 2017


FundersFunder number
David and Fela Shapell Family
Estate of Bernard Bishin
Georges Lustgarten Cancer Research Fund
Jaffe Bernard and Audrey Foundation
Jeanne and Joseph Nissim Foundation for Life Sciences Research
European Research Council310098
Israel Science Foundation


    • Egr3
    • Golgi tendon organ
    • Runx3
    • dorsal root ganglia
    • idiopathic scoliosis
    • mouse
    • muscle spindle
    • proprioception


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