Abstract
Scoliosis is a three-dimensional rotation of the spine that is defined as lateral curvature with a Cobb angle greater than 10 degrees. About 2–3% of the global population is affected by scoliosis, and more than 80% of scoliosis are caused by unknown factors (idiopathic). Adolescent idiopathic scoliosis is the most common type of scoliosis and occurs in children over 10 years, showing a female predominance. Of scoliosis patients, 10% have curve progression requiring medical interventions such as bracing and surgery. Scoliosis research has been delayed due to the genetic complexity and a lack of relevant animal models for functional studies; however, significant breakthroughs of scoliosis study have recently been made using zebrafish. The zebrafish is a powerful tool, owing to easy genetic manipulation and a natural susceptibility to spinal curvature. Here, we summarize the utility of zebrafish as a model system for human scoliosis.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Adham IM, Gille M, Gamel AJ, Reis A, Dressel R, Steding G et al (2005) The scoliosis (sco) mouse: a new allele of Pax1. Cytogenet Genome Res 111:16–26. https://doi.org/10.1159/000085665
Andersen MR, Farooq M, Koefoed K, Kjaer KW, Simony A, Christensen ST et al (2017) Mutation of the planar cell polarity gene VANGL1 in adolescent idiopathic scoliosis. Spine 42:E702–E707. https://doi.org/10.1097/BRS.0000000000001927
Azimzadeh J, Hergert P, Delouvee A, Euteneuer U, Formstecher E, Khodjakov A et al (2009) hPOC5 is a centrin-binding protein required for assembly of full-length centrioles. J Cell Biol 185(1):101–114. https://doi.org/10.1083/jcb.200808082
Baschal EE, Wethey CI, Swindle K, Baschal RM, Gowan K, Tang NLS et al (2014) Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis. G3 (Bethesda, Md.) 5:167–174. https://doi.org/10.1534/g3.114.015669
Bessa J, Tena JJ, de la Calle-Mustienes E, Fernandez-Minan A, Naranjo S, Fernandez A et al (2009) Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish. Dev Dyn 238(9):2409–2417. https://doi.org/10.1002/dvdy.22051
Bobyn JD, Little DG, Gray R, Schindeler A (2015) Animal models of scoliosis. J Orthop Res: Official Publication of the Orthopaedic Research Society 33:458–467. https://doi.org/10.1002/jor.22797
Brent AE, Tabin CJ (2002) Developmental regulation of somite derivatives: muscle, cartilage and tendon. Curr Opin Genet Dev 12(5):548–557
Brohmann H, Jagla K, Birchmeier C (2000) The role of Lbx1 in migration of muscle precursor cells. Development (Cambridge, England) 127:437–445
Buchan JG, Alvarado DM, Haller GE, Cruchaga C, Harms MB, Zhang T et al (2014) Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis. Hum Mol Genet 23:5271–5282. https://doi.org/10.1093/hmg/ddu224
Castelein RM, van Dieën JH, Smit TH (2005) The role of dorsal shear forces in the pathogenesis of adolescent idiopathic scoliosis – a hypothesis. Med Hypotheses 65:501–508. https://doi.org/10.1016/j.mehy.2005.03.025
Cheng JC, Castelein RM, Chu WC, Danielsson AJ, Dobbs MB, Grivas TB et al (2015) Adolescent idiopathic scoliosis. Nat Rev Dis Primers 1:15030. https://doi.org/10.1038/nrdp.2015.30
Choksi SP, Lauter G, Swoboda P, Roy S (2014) Switching on cilia: transcriptional networks regulating ciliogenesis. Development 141:1427–1441. https://doi.org/10.1242/dev.074666
Dahl E, Koseki H, Balling R (1997) Pax genes and organogenesis. BioEssays 19(9):755–765. https://doi.org/10.1002/bies.950190905
Fleming A, Keynes R, Tannahill D (2004) A central role for the notochord in vertebral patterning. Development 131(4):873–880. https://doi.org/10.1242/dev.00952
Gorman KF, Breden F (2009) Idiopathic-type scoliosis is not exclusive to bipedalism. Med Hypotheses 72:348–352. https://doi.org/10.1016/j.mehy.2008.09.052
Gorman KF, Tredwell SJ, Breden F (2007) The mutant guppy syndrome curveback as a model for human heritable spinal curvature. Spine 32:735–741. https://doi.org/10.1097/01.brs.0000259081.40354.e2
Gorman KF, Julien C d, Moreau A (2012) The genetic epidemiology of idiopathic scoliosis. Eur Spine J 21:1905–1919. https://doi.org/10.1007/s00586-012-2389-6
Grimes DT, Boswell CW, Morante NFC, Henkelman RM, Burdine RD, Ciruna B (2016) Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature. Science 352:1341–1344. https://doi.org/10.1126/science.aaf6419
Gross MK, Dottori M, Goulding M (2002) Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron 34:535–549
Guo L, Yamashita H, Kou I, Takimoto A, Meguro-Horike M, Horike S-i et al (2016) Functional investigation of a non-coding variant associated with adolescent idiopathic scoliosis in zebrafish: elevated expression of the ladybird Homeobox gene causes body axis deformation. PLoS Genet 12:e1005802. https://doi.org/10.1371/journal.pgen.1005802
Hayes M, Naito M, Daulat A, Angers S, Ciruna B (2013) Ptk7 promotes non-canonical Wnt/PCP-mediated morphogenesis and inhibits Wnt/β-catenin-dependent cell fate decisions during vertebrate development. Development (Cambridge, England) 140:1807–1818. https://doi.org/10.1242/dev.090183
Hayes M, Gao X, Yu LX, Paria N, Henkelman RM, Wise CA et al (2014) ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. Nat Commun 5:4777. https://doi.org/10.1038/ncomms5777
Hedequist D, Emans J (2007) Congenital scoliosis: a review and update. J Pediatr Orthop 27(1):106–116. https://doi.org/10.1097/BPO.0b013e31802b4993
Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N et al (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357(16):1608–1619. https://doi.org/10.1056/NEJMoa073687
Ikegawa S (2016) Genomic study of adolescent idiopathic scoliosis in Japan. Scoliosis Spinal Disord 11:5. https://doi.org/10.1186/s13013-016-0067-x
Justice CM, Bishop K, Carrington B, Mullikin JC, Swindle K, Marosy B et al (2016) Evaluation of IRX genes and conserved noncoding elements in a region on 5p13.3 linked to families with familial idiopathic scoliosis and kyphosis. G3 (Bethesda, Md.) 6:1707–1712. https://doi.org/10.1534/g3.116.029975
Karner CM, Long F, Solnica-Krezel L, Monk KR, Gray RS (2015) Gpr126/Adgrg6 deletion in cartilage models idiopathic scoliosis and pectus excavatum in mice. Hum Mol Genet 24(15):4365–4373. https://doi.org/10.1093/hmg/ddv170
Konieczny MR, Senyurt H, Krauspe R (2013) Epidemiology of adolescent idiopathic scoliosis. J Child Orthop 7:3–9. https://doi.org/10.1007/s11832-012-0457-4
Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J et al (2013) Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet 45(6):676–679. https://doi.org/10.1038/ng.2639
Kou I, Watanabe K, Takahashi Y, Momozawa Y, Khanshour A, Grauers A, Zhou H, Liu G, Fan Y-H, Takeda K, Ogura Y, Zhou T, Iwasaki Y, Kubo M, Wu Z, Matsumoto M, Einarsdottir E, Kere J, Huang D, Qiu G, Qiu Y, Wise CA, Song Y-Q, Wu N, Su P, Gerdhem P, Ikegawa S (2018) A multi-ethnic metaanalysis confirms the association of rs6570507 with adolescent idiopathic scoliosis. Sci Rep 8(1)
Levy DE, Darnell JE Jr (2002) Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 3(9):651–662. https://doi.org/10.1038/nrm909
Li W, Li Y, Zhang L, Guo H, Tian D, Li Y et al (2016) AKAP2 identified as a novel gene mutated in a Chinese family with adolescent idiopathic scoliosis. J Med Genet 53:488–493. https://doi.org/10.1136/jmedgenet-2015-103684
Liu Y, Sepich DS, Solnica-Krezel L (2017) Stat3/Cdc25a-dependent cell proliferation promotes embryonic axis extension during zebrafish gastrulation. PLoS Genet 13(2):e1006564. https://doi.org/10.1371/journal.pgen.1006564
Londono D, Kou I, Johnson TA, Sharma S, Ogura Y, Tsunoda T et al (2014) A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups. J Med Genet 51:401–406. https://doi.org/10.1136/jmedgenet-2013-102067
Lu X, Borchers AGM, Jolicoeur C, Rayburn H, Baker JC, Tessier-Lavigne M (2004) PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 430:93–98. https://doi.org/10.1038/nature02677
Miyagi C, Yamashita S, Ohba Y, Yoshizaki H, Matsuda M, Hirano T (2004) STAT3 noncell-autonomously controls planar cell polarity during zebrafish convergence and extension. J Cell Biol 166(7):975–981. https://doi.org/10.1083/jcb.200403110
Ogura Y, Kou I, Miura S, Takahashi A, Xu L, Takeda K et al (2015) A functional SNP in BNC2 is associated with adolescent idiopathic scoliosis. Am J Hum Genet 97(2):337–342. https://doi.org/10.1016/j.ajhg.2015.06.012
Ogura Y, Takeda K, Kou I, Khanshour A, Grauers A, Zhou H, Liu G, Fan Y-H, Zhou T, Wu Z, Takahashi Y, Matsumoto M, Einarsdottir E, Kere J, Huang D, Qiu G, Xu L, Qiu Y, Wise CA, Song Y-Q, Wu N, Su P, Gerdhem P, Watanabe K, Ikegawa S (2018) An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis. Sci Rep 8(1)
Ohata S, Alvarez-Buylla A (2016) Planar organization of multiciliated ependymal (E1) cells in the brain ventricular epithelium. Trends Neurosci 39:543–551. https://doi.org/10.1016/j.tins.2016.05.004
Ouellet J, Odent T (2013) Animal models for scoliosis research: state of the art, current concepts and future perspective applications. Eur Spine J: Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 22(Suppl 2):S81–S95. https://doi.org/10.1007/s00586-012-2396-7
Patten SA, Margaritte-Jeannin P, Bernard J-C, Alix E, Labalme A, Besson A et al (2015) Functional variants of POC5 identified in patients with idiopathic scoliosis. J Clin Invest 125:1124–1128. https://doi.org/10.1172/JCI77262
Patton EE, Zon LI (2001) The art and design of genetic screens: zebrafish. Nat Rev Genet 2:956–966. https://doi.org/10.1038/35103567
Peters H, Wilm B, Sakai N, Imai K, Maas R, Balling R (1999) Pax1 and Pax9 synergistically regulate vertebral column development. Development 126(23):5399–5408
Pourquie O (2011) Vertebrate segmentation: from cyclic gene networks to scoliosis. Cell 145(5):650–663. https://doi.org/10.1016/j.cell.2011.05.011
Schäfer K, Neuhaus P, Kruse J, Braun T (2003) The homeobox gene Lbx1 specifies a subpopulation of cardiac neural crest necessary for normal heart development. Circ Res 92:73–80
Shands AR Jr, Bundens WD (1956) Congenital deformities of the spine; an analysis of the roentgenograms of 700 children. Bull Hosp Joint Dis 17(2):110–133
Sharma S, Gao X, Londono D, Devroy SE, Mauldin KN, Frankel JT et al (2011) Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet 20:1456–1466. https://doi.org/10.1093/hmg/ddq571
Sharma S, Londono D, Eckalbar WL, Gao X, Zhang D, Mauldin K et al (2015) A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females. Nat Commun 6:6452. https://doi.org/10.1038/ncomms7452
Stickney HL, Barresi MJ, Devoto SH (2000) Somite development in zebrafish. Dev Dyn 219(3):287–303. https://doi.org/10.1002/1097-0177(2000)9999:9999<::AID-DVDY1065>3.0.CO;2-A.
Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N et al (2011) A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet 43(12):1237–1240. https://doi.org/10.1038/ng.974
Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N et al (1997) Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci U S A 94(8):3801–3804
Visel A, Minovitsky S, Dubchak I, Pennacchio LA (2007) VISTA enhancer browser – a database of tissue-specific human enhancers. Nucleic Acids Res 35:D88–D92. https://doi.org/10.1093/nar/gkl822
Wang WJ, Yeung HY, Chu WC-W, Tang NL-S, Lee KM, Qiu Y et al (2011) Top theories for the etiopathogenesis of adolescent idiopathic scoliosis. J Pediatr Orthop 31:S14–S27. https://doi.org/10.1097/BPO.0b013e3181f73c12
Witten PE, Huysseune A (2009) A comparative view on mechanisms and functions of skeletal remodelling in teleost fish, with special emphasis on osteoclasts and their function. Biol Rev Camb Philos Soc 84(2):315–346. https://doi.org/10.1111/j.1469-185X.2009.00077.x
Yamashita S, Miyagi C, Carmany-Rampey A, Shimizu T, Fujii R, Schier AF et al (2002) Stat3 controls cell movements during zebrafish gastrulation. Dev Cell 2(3):363–375
Zhu Z, Tang NL-S, Xu L, Qin X, Mao S, Song Y et al (2015) Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls. Nat Commun 6:8355. https://doi.org/10.1038/ncomms9355
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Guo, L., Ikegawa, S., Shukunami, C. (2018). Emergence of Zebrafish as a Model System for Understanding Human Scoliosis. In: Hirata, H., Iida, A. (eds) Zebrafish, Medaka, and Other Small Fishes. Springer, Singapore. https://doi.org/10.1007/978-981-13-1879-5_11
Download citation
DOI: https://doi.org/10.1007/978-981-13-1879-5_11
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-1878-8
Online ISBN: 978-981-13-1879-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)