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

被引：210

作者：

Grimes, D. T. ^{[1
]}

Boswell, C. W. ^{[2
,3
]}

Morante, N. F. C. ^{[1
]}

Henkelman, R. M. ^{[4
,5
]}

Burdine, R. D. ^{[1
]}

Ciruna, B. ^{[2
,3
]}

机构：

[1] Princeton Univ, Dept Mol Biol, Washington Rd, Princeton, NJ 08544 USA

[2] Hosp Sick Children, Program Dev & Stem Cell Biol, 686 Bay St, Toronto, ON M5G 0A4, Canada

[3] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

[4] Hosp Sick Children, Mouse Imaging Ctr, 25 Orde St, Toronto, ON M5T 3H7, Canada

[5] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada

来源：

SCIENCE | 2016年 / 352卷 / 6291期

基金：

加拿大健康研究院;

关键词：

PRIMARY CILIARY DYSKINESIA; PRIMARY CILIUM; SUSCEPTIBILITY; DOCKING;

D O I：

10.1126/science.aaf6419

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1341 / 1344

页数：4

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