@article{c0ffc1887f8d4ec2910a4d0fb563a242,
title = "Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature",
abstract = "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.",
author = "Grimes, {D. T.} and Boswell, {C. W.} and Morante, {N. F.C.} and Henkelman, {R. M.} and Burdine, {R. D.} and B. Ciruna",
note = "Funding Information: We gratefully acknowledge E. Lee, D. Holmyard, P. Paroutis, and L. Yu for technical assistance; A. Morley, A. Ng, C. Hasty, D. Bosco, and P. Johnson for zebrafish care; and J. Schottenfeld-Roames and T. Ku for initial observations of spine curvatures in c21orf59TS mutant fish. This work was supported in part by funding from the Canada Research Chairs program to R.M.H. and B.C.; National Institute of Child Health and Development grant 2R01HD048584 to R.D.B.; and Canadian Institutes of Health Research (MOP-111075) and March of Dimes Foundation (#1-FY13-398) grants to B.C. D.T.G., C.W.B., and N.F.C.M. performed all experiments characterizing scoliosis phenotypes. C.W.B. cloned and characterized foxj1a transgenic lines. N.F.C.M. generated the dyx1c1pr13 allele. C.W.B. and R.M.H. performed μCT. B.C. and C.W.B. performed SEM and CSF flow analyses. D.T.G., C.W.B., N.F.C.M., R.D.B., and B.C. analyzed the data. D.T.G., C.W.B. and B.C. wrote the manuscript, and all authors edited the manuscript. Publisher Copyright: {\textcopyright} 2016, American Association for the Advancement of Science. All rights reserved.",
year = "2016",
month = jun,
day = "10",
doi = "10.1126/science.aaf6419",
language = "English (US)",
volume = "352",
pages = "1341--1344",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6291",
}