Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish.
Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish.
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室室极性缺陷以及斑马鱼中混乱的睫毛跳动驱动器异常的脑脊液流动和脊柱曲率异常。
DOI：
10.1371/journal.pbio.3002008
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发表时间：
2023-03
期刊：
影响因子：
9.8
通讯作者：
Zhao, Chengtian
中科院分区：
文献类型：
--
作者：
Xie, Haibo;Kang, Yunsi;Liu, Junjun;Huang, Min;Dai, Zhicheng;Shi, Jiale;Wang, Shuo;Li, Lanqin;Li, Yuan;Zheng, Pengfei;Sun, Yi;Han, Qize C.;Zhang, Jingjing;Zhu, Zezhang;Xu, Leilei;Yelick, Pamela;Cao, Muqing;Zhao, Chengtian
Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression. Idiopathic scoliosis is the most common spinal deformity diagnosed in childhood or early adolescence. A zebrafish model of scoliosis due to abnormal ciliary beating and ependymal polarity defects reveals that uneven distribution of Urotensin neuropeptides is a major cause of spinal curvature; abnormal Urotensin signaling is also observed in human idiopathic scoliosis patients.
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影响因子：
5.8
作者：
Alejevski F;Leemans M;Gaillard AL;Leistenschneider D;de Flori C;Bougerol M;Le Mével S;Herrel A;Fini JB;Pézeron G;Tostivint H
通讯作者：
Tostivint H
特发性脊柱侧弯的斑马鱼模型将脑脊液流缺陷与脊柱曲率联系起来。
DOI：
10.1126/science.aaf6419
发表时间：
2016-06-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Grimes DT;Boswell CW;Morante NF;Henkelman RM;Burdine RD;Ciruna B
通讯作者：
Ciruna B
DOI：
10.1038/nrn3921
发表时间：
2015-08
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Lun MP;Monuki ES;Lehtinen MK
通讯作者：
Lehtinen MK
影响因子：
9.2
作者：
Cantaut-Belarif, Yasmine;Sternberg, Jenna R.;Bardet, Pierre-Luc
通讯作者：
Bardet, Pierre-Luc
影响因子：
4.3
作者：
Henson, Hannah E.;Parupalli, Chaithanyarani;Taylor, Michael R.
通讯作者：
Taylor, Michael R.