Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature

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Science  10 Jun 2016:
Vol. 352, Issue 6291, pp. 1341-1344
DOI: 10.1126/science.aaf6419

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Altered fluid flow causes curved spine

Adolescent idiopathic scoliosis is characterized by three-dimensional spinal curves and affects 3% of the world's children. However, the biological basis of this condition is unclear. Grimes et al. studied zebrafish models that likewise display a curved spine. Defects in the formation and function of motile cilia in the central nervous system perturbed the flow of cerebrospinal fluid (CSF), leading to abnormal spinal curvatures as the fish grew. Curves could be partially rescued by restoring CSF flow, suggesting potential therapeutic strategies if the same mechanism is shared in humans.

Science, this issue p. 1341


Idiopathic scoliosis (IS) affects 3% of children worldwide, yet the mechanisms underlying this spinal deformity remain unknown. Here we show that ptk7 mutant zebrafish, a faithful developmental model of IS, exhibit defects in ependymal cell cilia development and cerebrospinal fluid (CSF) flow. Transgenic reintroduction of Ptk7 in motile ciliated lineages prevents scoliosis in ptk7 mutants, and mutation of multiple independent cilia motility genes yields IS phenotypes. We define a finite developmental window for motile cilia in zebrafish spine morphogenesis. Notably, restoration of cilia motility after the onset of scoliosis blocks spinal curve progression. Together, our results indicate a critical role for cilia-driven CSF flow in spine development, implicate irregularities in CSF flow as an underlying biological cause of IS, and suggest that noninvasive therapeutic intervention may prevent severe scoliosis.

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