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

Publication date: 21 August 2017
Source:Developmental Cell, Volume 42, Issue 4
Author(s): 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
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.

Graphical abstract

Teaser

Blecher et al. report that mutant mice lacking functional proprioceptive circuitry develop peripubertal scoliosis not preceded by vertebral dysplasia or muscle asymmetry. Knockout mice lacking one of two proprioceptor types displayed the same, but less severe, phenotype. These findings uncover a central role for proprioception in maintaining spinal alignment.


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