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Developmental and Functional Anatomy of the Spine

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The Genetics and Development of Scoliosis

Abstract

The vertebral column is composed of alternating vertebrae and intervertebral discs and is supported by spinal ligaments and muscles. All of these components are essential to the structural integrity of the spine, which plays a vital role in protecting the spinal cord, transmitting the weight of the body, and providing a flexible axis for head and torso movements. The degree of movement of the vertebrae varies between the cervical, thoracic, lumbar, and sacrococcygeal regions of the spine. The thoracic and sacrococcygeal curvatures are established during the fetal period while the cervical and thoracic curvatures develop during infancy. Congenital defects and degenerative diseases can result in exaggerated, abnormal curvatures. The most common of these include kyphosis (hunchback deformity), lordosis (swayback deformity), and scoliosis. To appreciate the potential underlying causes of scoliosis, we must understand the highly orchestrated morphogenetic events that specify and pattern the spinal elements that are derived from a common embryonic origin in the paraxial mesoderm. Here, we review the functional anatomy of the spine and our current understanding of the underlying genetic regulation of its development, including the formation of the vertebrae, intervertebral discs, and spinal muscles and tendons.

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References

  1. Alexander MA, Season EH. Idiopathic scoliosis: an electromyographic study. Arch Phys Med Rehabil. 1978;59:314–5.

    PubMed  CAS  Google Scholar 

  2. Alvares LE, Schubert FR, Thorpe C, Mootoosamy RC, Cheng L, Parkyn G, et al. Intrinsic, Hox-dependent cues determine the fate of skeletal muscle precursors. Dev Cell. 2003;5:379–90.

    Article  PubMed  CAS  Google Scholar 

  3. Aoyama H, Asamoto K. The developmental fate of the rostral/caudal half of a somite for vertebra and rib formation: experimental confirmation of the resegmentation theory using chick-quail chimeras. Mech Dev. 2000;99:71–82.

    Article  PubMed  CAS  Google Scholar 

  4. Arnold HH, Braun T. Genetics of muscle determination and development. Curr Top Dev Biol. 2000;48:129–64.

    Article  PubMed  CAS  Google Scholar 

  5. Asahara H, Inui M, Lotz MK. Tendon and ligaments: connecting development biology to musculoskeletal disease pathogenesis. J Bone Miner Res. 2017;32:1773–82.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ashby P, Chinnah T, Zakany J, Duboule D, Tickle C. Muscle and tendon pattern is altered independently of skeletal pattern in HoxD mutant limbs. J Anat. 2002;201:422.

    PubMed  PubMed Central  CAS  Google Scholar 

  7. Avikainen VJ, Rezasoltani A, Kauhanen HA. Asymmetry of paraspinal EMG-time characteristics in idiopathic scoliosis. J Spinal Disord. 1999;12:61–7.

    Article  PubMed  CAS  Google Scholar 

  8. Baffi MO, Moran MA, Serra R. Tgfbr2 regulates the maintenance of boundaries in the axial skeleton. Dev Biol. 2006;296:363–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Barrallo-Gimeno A, Nieto MA. The snail genes as inducers of cell movement and survival: implications in development and cancer. Development. 2005;132:3151–61.

    Article  PubMed  CAS  Google Scholar 

  10. Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000;2:84–9.

    Article  PubMed  CAS  Google Scholar 

  11. Berkes CA, Bergstrom DA, Penn BH, Seaver KJ, Knoepfler PS, Tapscott SJ. Pbx marks genes for activation by MyoD indicating a role for a homeodomain protein in establishing myogenic potential. Mol Cell. 2004;14:465–77.

    Article  PubMed  CAS  Google Scholar 

  12. Borello U, Berarducci B, Murphy P, Bajard L, Buffa V, Piccolo S, et al. The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis. Development. 2006;133:3723–32.

    Article  PubMed  CAS  Google Scholar 

  13. Borycki AG, Brunk B, Tajbakhsh S, Buckingham M, Chiang C, Emerson CP Jr. Sonic hedgehog controls epaxial muscle determination through Myf5 activation. Development. 1999;126:4053–63.

    PubMed  CAS  Google Scholar 

  14. Borycki A, Brown AM, Emerson CP Jr. Shh and Wnt signaling pathways converge to control Gli gene activation in avian somites. Development. 2000;127:2075–87.

    PubMed  CAS  Google Scholar 

  15. Brand-Saberi B, Christ B. Evolution and development of distinct cell lineages derived from somites. Curr Top Dev Biol. 2000;48:1–42.

    PubMed  CAS  Google Scholar 

  16. Brent AE, Tabin CJ. FGF acts directly on the somitic tendon progenitors through the Ets transcription factors Pea3 and Erm to regulate scleraxis expression. Development. 2004;131:3885–96.

    Article  PubMed  CAS  Google Scholar 

  17. Brent AE, Schweitzer R, Tabin CJ. A somitic compartment of tendon progenitors. Cell. 2003;113:235–48.

    Article  PubMed  CAS  Google Scholar 

  18. Brent AE, Braun T, Tabin CJ. Genetic analysis of interactions between the somitic muscle, cartilage and tendon cell lineages during mouse development. Development. 2005;132:515–28.

    Article  PubMed  CAS  Google Scholar 

  19. Buchberger A, Seidl K, Klein C, Eberhardt H, Arnold HH. cMeso-1, a novel bHLH transcription factor, is involved in somite formation in chicken embryos. Dev Biol. 1998;199:201–15.

    Article  PubMed  CAS  Google Scholar 

  20. Burgess R, Cserjesi P, Ligon KL, Olson EN. Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and developing somites. Dev Biol. 1995;168:296–306.

    Article  PubMed  CAS  Google Scholar 

  21. Burgess R, Rawls A, Brown D, Bradley A, Olson EN. Requirement of the paraxis gene for somite formation and musculoskeletal patterning. Nature. 1996;384:570–3.

    Article  PubMed  CAS  Google Scholar 

  22. Butterworth TR, James C. Electromyographic studies in idiopathic scoliosis. South Med J. 1969;62:1008–10.

    Article  PubMed  Google Scholar 

  23. Buxton DF, Peck D. Neuromuscular spindles relative to joint movement complexities. Clin Anat. 1989;2:211–24.

    Article  Google Scholar 

  24. Bylund P, Jansson E, Dahlberg E, Eriksson E. Muscle fiber types in thoracic erector spinae muscles. Clin Orthop. 1987;214:222–8.

    Google Scholar 

  25. Cailliet R. Low back pain syndrome. 4th ed. Philadelphia: FA Davis Company; 1988.

    Google Scholar 

  26. Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, et al. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2:76–83.

    Article  PubMed  CAS  Google Scholar 

  27. Capellini TD, Di Giacomo G, Salsi V, Brendolan A, Ferretti E, Srivastava D, et al. Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression. Development. 2006;133:2263–73.

    Article  PubMed  CAS  Google Scholar 

  28. Capellini TD, Zewdu R, Di Giacomo G, Asciutti S, Kugler JE, Di Gregorio A, et al. Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome. Dev Biol. 2008;321:500–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Chal J, Guillot C, Pourquié O. PAPC couples the segmentation clock to somite morphogenesis by regulating N-cadherin-dependent adhesion. Development. 2017;144:664–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Chan YL, Cheng JCY, Guo X, King AD, Griffith JF, Metreweli C. MRI evaluation of multifidus muscles in adolescent idiopathic scoliosis. Pediatr Radiol. 1999;29:360–3.

    Article  PubMed  CAS  Google Scholar 

  31. Chen F, Greer J, Capecchi MR. Analysis of Hoxa7/Hoxb7 mutants suggests periodicity in the generation of different sets of vertebrae. Mech Dev. 1998;77:49–57.

    Article  PubMed  CAS  Google Scholar 

  32. Cheung J, Halbertsma JPK, Veldhuizen AG, Sluiter WJ, Maurits NM, Cool JC, et al. A preliminary study on electromyographic analysis of the paraspinal musculature in idiopathic scoliosis. Eur Spine J. 2005;14:130–7.

    Article  PubMed  Google Scholar 

  33. Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature. 1996;383:407–13.

    Article  PubMed  CAS  Google Scholar 

  34. Choi KS, Harfe BD. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs. Proc Natl Acad Sci U S A. 2011;108:9484–9.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Choi KS, Lee C, Harfe BD. Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs. Mech Dev. 2012;129:255–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Christ B, Wilting J. From somites to vertebral column. Ann Anat. 1992;174:23–32.

    Article  PubMed  CAS  Google Scholar 

  37. Condie BG, Capecchi MR. Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions. Science. 1994;370:304–7.

    CAS  Google Scholar 

  38. Correia KM, Conlon RA. Surface ectoderm is necessary for the morphogenesis of somites. Mech Dev. 2000;91:19–30.

    Article  PubMed  CAS  Google Scholar 

  39. Cossu G, Borello U. Wnt signaling and the activation of myogenesis in mammals. EMBO J. 1999;18:6867–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Dale JK, Malapert P, Chal J, Vilhais-Neto G, Maroto M, Johnson T, Jayasinghe S, Trainor P, Herrmann B, Pourquié O. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Dev Cell. 2006;10:355–66.

    Article  PubMed  CAS  Google Scholar 

  41. de la Pompa JL, Wakeham A, Correia KM, Samper E, Brown S, Aguilera RJ, et al. Conservation of the Notch signaling pathway in mammalian neurogenesis. Development. 1997;124:1139–48.

    PubMed  Google Scholar 

  42. Denetclaw WF Jr, Ordahl CP. The growth of the dermomyotome and formation of early myotome lineages in thoracolumbar somites of chicken embryos. Development. 2000;127:893–905.

    PubMed  CAS  Google Scholar 

  43. Denetclaw WF Jr, Christ B, Ordahl CP. Location and growth of epaxial myotome precursor cells. Development. 1997;124:1601–10.

    PubMed  CAS  Google Scholar 

  44. Dockter JL. Sclerotome induction and differentiation. Curr Top Dev Biol. 2000;48:77–127.

    Article  PubMed  CAS  Google Scholar 

  45. Duband JL, Dufour S, Hatta K, Takeichi M, Edelman GM, Thiery JP. Adhesion molecules during somitogenesis in the avian embryo. J Cell Biol. 1987;104:1361–74.

    Article  PubMed  CAS  Google Scholar 

  46. Dubrulle J, Pourquié O. Coupling segmentation to axis formation. Development. 2004;131:5783–93.

    Article  PubMed  CAS  Google Scholar 

  47. Dunwoodie SL, Henrique D, Harrison SM, Beddington RSP. Mouse Dll3: a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo. Development. 1997;124:3065–76.

    PubMed  CAS  Google Scholar 

  48. Eloy-Trinquet S, Wang H, Edom-Vovar F, Duprez D. Fgf signaling components are associated with muscles and tendons during limb development. Dev Dyn. 2009;238:1195–206.

    Article  PubMed  CAS  Google Scholar 

  49. Fan CM, Tessier-Lavigne M. Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog. Cell. 1994;79:1175–86.

    Article  PubMed  CAS  Google Scholar 

  50. Fidler MW, Jowett RL. Muscle imbalance in the aetiology of scoliosis. J Bone Joint Surg. 1976;58-B:200–1.

    Article  Google Scholar 

  51. Fisher RE, Smith HF, Kusumi K, Tassone EE, Rawls A, Wilson-Rawls J. Mutations in the Notch pathway alter the patterning of multifidus. Anat Rec. 2012;295:32–9.

    Article  Google Scholar 

  52. Ford DM, Bagnall KM, McFadden KD, Greenhill BJ, Raso VJ. Paraspinal muscle imbalance in adolescent idiopathic scoliosis. Spine. 1984;9:373–6.

    Article  PubMed  CAS  Google Scholar 

  53. Furumoto TA, Miura N, Akasaka T, Mizutanikoseki Y, Sudo H, Fukuda K, et al. Notochord-dependent expression of MFH1 and PAX1 cooperates maintain the proliferation of sclerotome cells during the vertebral column development. Dev Biol. 1999;210:15–29.

    Article  PubMed  CAS  Google Scholar 

  54. Gaut L, Robert N, Delalande A, Bonnin MA, Pichon C, Duprez D. EGR1 regulates transcription downstream of mechanical signals during tendon formation and healing. PLoS One. 2016;11:e0166237.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Geetha-Loganathan P, Nimmagadda S, Huang R, Christ B, Scaal M. Regulation of ectodermal Wnt6 expression by the neural tube is transduced by dermomyotomal Wnt11: a mechanism of dermomyotomal lip sustainment. Development. 2006;133:2897–904.

    Article  PubMed  CAS  Google Scholar 

  56. Goldstein RS, Kalcheim C. Determination of epithelial half-somites in skeletal morphogenesis. Development. 1992;116:441–5.

    PubMed  CAS  Google Scholar 

  57. Henry CA, Hall LA, Burr Hille M, Solnica-Krezel L, Cooper MS. Somites in zebrafish doubly mutant for knypek and trilobite form without internal mesenchymal cells or compaction. Curr Biol. 2000;10:1063–6.

    Article  PubMed  CAS  Google Scholar 

  58. Horikawa K, Radice G, Takeichi M, Chisaka O. Adhesive subdivisions intrinsic to the epithelial somites. Dev Biol. 1999;215:182–9.

    Article  PubMed  CAS  Google Scholar 

  59. Hrabĕ de Angelis M, McIntyre J 2nd, Gossler A. Maintenance of somite borders in mice requires the Delta homologue DII1. Nature. 1997;386:717–21.

    Article  PubMed  Google Scholar 

  60. Huang R, Zhi Q, Neubuser A, Muller TS, Brand-Saberi B, Christ B, et al. Function of somite and somitocoele cells in the formation of the vertebral motion segment in avian embryos. Acta Anat. 1996;155:231–41.

    Article  PubMed  CAS  Google Scholar 

  61. Jacob HJ, Christ B. On the formation of muscular pattern in the chick limb. In: Teratology of the limbs. Berlin: Walter de Gruyter and Co.; 1988. p. 89–97.

    Google Scholar 

  62. Jacob M, Jacob JH, Christ B. The early differentiation of the perinotochordal connective tissue. A scanning and transmission electron microscopic study on chick embryos. Experientia. 1975;31:1083–6.

    Article  PubMed  CAS  Google Scholar 

  63. Jeong Y, Epstein DJ. Distinct regulators of Shh transcription in the floor plate and notochord indicate separate origins for these tissues in the mouse node. Development. 2003;130:3891–902.

    Article  PubMed  CAS  Google Scholar 

  64. Jiang YJ, Aerne BL, Smithers L, Haddon C, Ish-Horowicz D, Lewis J. Notch signaling and the synchronization of the somite segmentation clock. Nature. 2000;408:475–9.

    Article  PubMed  CAS  Google Scholar 

  65. Johnson J, Rhee J, Parsons SM, Brown D, Olson EN, Rawls A. The anterior/posterior polarity of somites is disrupted in paraxis-deficient mice. Dev Biol. 2001;229:176–87.

    Article  PubMed  CAS  Google Scholar 

  66. Kahane N, Cinnamon Y, Kalcheim C. The cellular mechanism by which the dermomyotome contributes to the second wave of myotome development. Development. 1998;125:4259–71.

    PubMed  CAS  Google Scholar 

  67. Kalson NS, Lu Y, Taylor SH, Starborg T, Homes DF, Kadler KE. A structure-based extracellular matrix expansion mechanism of fibrous tissue growth. elife. 2015;4:e05958.

    Article  PubMed Central  Google Scholar 

  68. Kardon G, Harfe BD, Tabin CT. A Tcf4-positive mesodermal population provides a prepattern for vertebrate limb muscle patterning. Dev Cell. 2015;5:937–44.

    Article  Google Scholar 

  69. Kayama T, Mori M, Ito Y, Matsushima T, Nakamichi R, Suzuki H, et al. Gtf2ird1-dependent Mohawk expression regulates Mechanosensing properties of the tendon. Mol Cell Biol. 2016;36:1297–309.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Keynes RJ, Stern CD. Mechanisms of vertebrate segmentation. Development. 1988;103:413–29.

    PubMed  CAS  Google Scholar 

  71. Khosla S, Tredwell SJ, Day B, Shinn SL, Ovalle WK. An ultrastructural study of multifidus muscle in progressive idiopathic scoliosis-changes resulting from a sarcolemmal defect of the myotendinous junction. J Neurol Sci. 1980;46:13–31.

    Article  PubMed  CAS  Google Scholar 

  72. Kim SY, Paylor SW, Magnuson T, Schumacher A. Juxtaposed Polycomb complexes co-regulate vertebral identity. Development. 2006;133:4957–68.

    Article  PubMed  CAS  Google Scholar 

  73. Koizumi K, Nakajima M, Yuasa S, Saga Y, Sakai T, Kuriyama T, et al. The role of presenilin 1 during somite segmentation. Development. 2001;128:1391–402.

    PubMed  CAS  Google Scholar 

  74. Kulesa PM, Fraser SE. Cell dynamics during somite boundary formation revealed by time-lapse analysis. Science. 2002;298:991–5.

    Article  PubMed  CAS  Google Scholar 

  75. Kulesa PM, Schnell S, Rudloff S, Baker RE, Maini PK. From segment to somite: segmentation epithelialization analyzed within quantitative frameworks. Dev Dyn. 2007;236:1392–402.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Kusumi K, Sun ES, Kerrebrock AW, Bronson RT, Chi DC, Bulotsky MS, et al. The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries. Nat Genet. 1998;19:274–8.

    Article  PubMed  CAS  Google Scholar 

  77. Lewis EB. A gene complex controlling segmentation in Drosophila. Nature. 1978;276:565–70.

    Article  PubMed  CAS  Google Scholar 

  78. Li J, Yoon ST, Hutton WC. Effect of bone morphogenetic protein-2 (BMP-2) on matrix production, other BMPs, and BMP receptors in rat intervertebral disc cells. J Spinal Disord Tech. 2004;17:423–8.

    Article  PubMed  Google Scholar 

  79. Linask KK, Ludwig C, Han MD, Liu X, Radice GL, Knudsen KA. N-cadherin/catenin-mediated morphoregulation of somite formation. Dev Biol. 1998;202:85–102.

    Article  PubMed  CAS  Google Scholar 

  80. Linker C, Lesbros C, Gros J, Burrus LW, Rawls A, Marcelle C. Beta-catenin-dependent Wnt signalling controls the epithelial organisation of somites through the activation of paraxis. Development. 2005;132:3895–905.

    Article  PubMed  CAS  Google Scholar 

  81. Mackie EJ, Ahmed YA, Tatarczuch L, Chen KS, Mirams M. Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol. 2008;40:46–62.

    Article  PubMed  CAS  Google Scholar 

  82. Maconochie MK, Nonchev S, Studer M, Chan SK, Popperl H, Sham MH, et al. Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1. Genes Dev. 1997;11:1885–95.

    Article  PubMed  CAS  Google Scholar 

  83. Maier JA, Lo Y, Harfe BD. Foxa1 and Foxa2 are required for formation of the intervertebral discs. PLoS One. 2013;8:e55528.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Mankoo BS, Skuntz S, Harrigan I, Grigorieva E, Candia A, Wright CV, et al. The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites. Development. 2003;130:4655–64.

    Article  PubMed  CAS  Google Scholar 

  85. Mannion AF, Meier M, Grob D, Müntener M. Paraspinal muscle fibre type alterations associated with scoliosis: an old problem revisited with new evidence. Eur Spine J. 1998;7:289–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Mansouri A, Pla P, Larue L, Gruss P. Pax3 acts cell autonomously in the neural tube and somites by controlling cell surface properties. Development. 2001;128:1995–2005.

    PubMed  CAS  Google Scholar 

  87. McDermott A, Gustafsson M, Elsam T, Hui CC, Emerson CP Jr, Borycki AG. Gli2 and Gli3 have redundant and context-dependent function in skeletal muscle formation. Development. 2005;132:345–57.

    Article  PubMed  CAS  Google Scholar 

  88. McIntyre DM, Rakshit S, Yallowitz AR, Loken L, Jeannotte L, Capecchi MR, et al. Hox patterning of the vertebrate rib cage. Development. 2007;134:2981–9.

    Article  PubMed  CAS  Google Scholar 

  89. McKinsey TA, Zhang CL, Lu J, Olson EN. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature. 2000;408:106–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. McKinsey TA, Zhang CL, Olson EN. Control of muscle development by dueling HATs and HDACs. Curr Opin Genet Dev. 2001;11:497–504.

    Article  PubMed  CAS  Google Scholar 

  91. McMahon JA, Takada S, Zimmerman LB, McMahon AP. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev. 1998;12:1438–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Meier MP, Klein MP, Krebs D, Grob D, Müntener M. Fiber transformations in multifidus muscle of young patients with idiopathic scoliosis. Spine. 1997;22:2357–64.

    Article  PubMed  CAS  Google Scholar 

  93. Mendias CL, Gumucio JP, Bakhurin KI, Lynch EB, Brooks SV. Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts. J Orthop Res. 2012;30:606–12.

    Article  PubMed  CAS  Google Scholar 

  94. Mercer SR, Bogduk N. Clinical anatomy of ligamentum nuchae. Clin Anat. 2003;16:484–93.

    Article  PubMed  Google Scholar 

  95. Mittapalli VR, Huang R, Patel K, Christ B, Scaal M. Arthrotome: a specific joint forming compartment in the avian somite. Dev Dyn. 2005;234:48–53.

    Article  PubMed  Google Scholar 

  96. Moens CB, Selleri L. Hox cofactors in vertebrate development. Dev Biol. 2006;291:193–206.

    Article  PubMed  CAS  Google Scholar 

  97. Molkentin JD, Olson EN. Defining the regulatory networks for muscle development. Curr Opin Genet Dev. 1996;6:445–53.

    Article  PubMed  CAS  Google Scholar 

  98. Monsoro-Burq AH, Bontoux M, Teillet MA, Le Douarin NM. Heterogeneity in the development of the vertebra. Proc Natl Acad Sci U S A. 1994;91:10435–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Monsoro-Burq AH, Duprez D, Watanabe Y, Bontoux M, Vincent C, Brickell P, et al. The role of bone morphogenetic proteins in vertebral development. Development. 1996;122:3607–16.

    PubMed  CAS  Google Scholar 

  100. Moore KL, Dalley AF. Clinically oriented anatomy. Baltimore: Lippincott Williams and Wilkins; 2006.

    Google Scholar 

  101. Morimoto M, Sasaki N, Oginuma M, Kiso M, Igarashi K, Aizaki K, et al. The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite. Development. 2007;134:1561–9.

    Article  PubMed  CAS  Google Scholar 

  102. Murchison ND, Price BA, Conner DA, Keene DR, Olson EN, Tabin CJ, et al. Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons. Development. 2007;134:2697–708.

    Article  PubMed  CAS  Google Scholar 

  103. Nakaya Y, Kuroda S, Katagiri YT, Kaibuchi K, Takahashi Y. Mesenchymal-epithelial transition during somitic segmentation is regulated by differential roles of Cdc42 and Rac1. Dev Cell. 2004;7:425–38.

    Article  PubMed  CAS  Google Scholar 

  104. Oka C, Nakano T, Wakeham A, de la Pompa JL, Mori C, Sakai T, et al. Disruption of the mouse RBP-J kappa gene results in early embryonic death. Development. 1995;121:3291–301.

    PubMed  CAS  Google Scholar 

  105. Ordahl CP, Le Douarin NM. Two myogenic lineages within the developing somite. Development. 1992;114:339–53.

    PubMed  CAS  Google Scholar 

  106. Ordahl CP, Berdougo E, Venters SJ, Denetclaw WF Jr. The dermomyotome dorsomedial lip drives growth and morphogenesis of both the primary myotome and dermomyotome epithelium. Development. 2001;128:1731–44.

    PubMed  CAS  Google Scholar 

  107. Paavola LG, Wilson DB, Center EM. Histochemistry of the developing notochord, perichordal sheath and vertebrae in Danforth's short-tail (sd) and normal C57BL/6 mice. J Embryol Exp Morphol. 1980;55:227–45.

    PubMed  CAS  Google Scholar 

  108. Palmeirim I, Dubrulle J, Henrique D, Ish-Horowicz D, Pourquié O. Uncoupling segmentation and somitogenesis in the chick presomitic mesoderm. Dev Genet. 1998;23:77–85.

    Article  PubMed  CAS  Google Scholar 

  109. Peschiaroli A, Figliola R, Coltella L, Strom A, Valentini A, D’Agnano I, et al. MyoD induces apoptosis in the absence of RB function through a p21(WAF1)-dependent re-localization of cyclin/cdk complexes to the nucleus. Oncogene. 2002;21:8114–27.

    Article  PubMed  CAS  Google Scholar 

  110. Peters H, Doll U, Niessing J. Differential expression of the chicken Pax-1 and Pax-9 gene: in situ hybridization and immunohistochemical analysis. Dev Dyn. 1995;203:1–16.

    Article  PubMed  CAS  Google Scholar 

  111. Peters H, Wilm B, Sakai N, Imai K, Maas R, Balling R. Pax1 and Pax9 synergistically regulate vertebral column development. Development. 1999;126:5399–408.

    PubMed  CAS  Google Scholar 

  112. Popperl H, Bienz M, Studer M, Chan SK, Aparicio S, Brenner S, et al. Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell. 1995;81:1031–42.

    Article  PubMed  CAS  Google Scholar 

  113. Pourquie O, Coltey M, Teillet MA, Ordahl C, Le Douarin M. Control of dorsoventral patterning of somitic derivatives by notochord and floor plate. Proc Natl Acad Sci U S A. 1993;90:5242–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Pryce B, Watson SS, Murchison ND, Staverosky JA, Dunker N, Schweitzer R. Recruitment and maintenance of tendon progenitors by TGFbeta signaling are essential for tendon formation. Development. 2009;136:1351–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Puri PL, Sartorelli V, Yang XJ, Hamamori Y, Ogryzko VV, Howard BH, et al. Differential roles of p300 and PCAF acetyltransferases in muscle differentiation. Mol Cell. 1997;1:35–45.

    Article  PubMed  CAS  Google Scholar 

  116. Radice GL, Rayburn H, Matsunami H, Knudsen KA, Takeichi M, Hynes RO. Developmental defects in mouse embryos lacking N-cadherin. Dev Biol. 1997;181:64–78.

    Article  PubMed  CAS  Google Scholar 

  117. Reshef R, Maroto M, Lassar AB. Regulation of dorsal somitic cell fates: BMPs and Noggin control the timing and pattern of myogenic regulator expression. Genes Dev. 1998;12:290–303.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Reuber M, Schultz A, McNeill T, Spencer D. Trunk muscle myoelectric activities in idiopathic scoliosis. Spine. 1983;8:447–56.

    Article  PubMed  CAS  Google Scholar 

  119. Rhee J, Takahashi Y, Saga Y, Wilson-Rawls J, Rawls A. The protocadherin papc is involved in the organization of the epithelium along the segmental border during mouse somitogenesis. Dev Biol. 2003;254:248–61.

    Article  PubMed  CAS  Google Scholar 

  120. Riddle HF, Roaf R. Muscle imbalance in the causation of scoliosis. Lancet. 1955;268:1245–7.

    Article  PubMed  CAS  Google Scholar 

  121. Rodrigo I, Hill RE, Balling R, Münsterberg A, Imai K. Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Development. 2003;130:473–82.

    Article  PubMed  CAS  Google Scholar 

  122. Rodrigo I, Bovolenta P, Mankoo BS, Imai K. Meox homeodomain proteins are required for Bapx1 expression in the sclerotome and activate its transcription by direct binding to its promoter. Mol Cell Biol. 2004;24:2757–566.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Rowton M, Ramos P, Anderson DM, Rhee JM, Cunliffe HE, Rawls A. Regulation of mesenchymal-to-epithelial transition by Paraxis during somitogenesis. Dev Dyn. 2013;242:1332–44.

    Article  PubMed  CAS  Google Scholar 

  124. Saga Y, Hata N, Koseki H, Taketo MM. Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation. Genes Dev. 1997;11:1827–39.

    Article  PubMed  CAS  Google Scholar 

  125. Sahgal V, Shah A, Flanagan N, Schaffer M, Kane W, Subramani V, et al. Morphologic and morphometric studies of muscle in idiopathic scoliosis. Acta Orthop. 1983;54:242–51.

    Article  CAS  Google Scholar 

  126. Sartorelli V, Puri PL, Hamamori Y, Ogryzko V, Chung G, Nakatani Y, et al. Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program. Mol Cell. 1999;4:725–34.

    Article  PubMed  CAS  Google Scholar 

  127. Sato Y, Takahashi Y. A novel signal induces a segmentation fissure by acting in a ventral-to-dorsal direction in the presomitic mesoderm. Dev Biol. 2005;282:183–91.

    Article  PubMed  CAS  Google Scholar 

  128. Sato Y, Yasuda K, Takahashi Y. Morphological boundary forms by a novel inductive event mediated by Lunatic fringe and Notch during somitic segmentation. Development. 2002;129:3633–44.

    PubMed  CAS  Google Scholar 

  129. Schmidt C, Stoeckelhuber M, McKinnell I, Putz R, Christ B, Patel K. Wnt 6 regulates the epithelialisation process of the segmental plate mesoderm leading to somite formation. Dev Biol. 2004;271:198–209.

    Article  PubMed  CAS  Google Scholar 

  130. Schubert FR, Tremblay P, Mansouri A, Faisst AM, Kammandel B, Lumsden A, et al. Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites. Dev Dyn. 2001;222:506–21.

    Article  PubMed  CAS  Google Scholar 

  131. Schuster-Gossler K, Harris B, Johnson R, Serth J, Gossler A. Notch signalling in the paraxial mesoderm is most sensitive to reduced Pofut1 levels during early mouse development. BMC Dev Biol. 2009;9:6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Schweitzer R, Chyung JH, Murtaugh LC, Brent AE, Rosen V, Olson EN, et al. Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments. Development. 2001;128:3855–66.

    PubMed  CAS  Google Scholar 

  133. Schweitzer R, Zelzer E, Volk T. Connecting muscles to tendons: tendons and musculoskeletal development in flies and vertebrates. Development. 2010;137(17):2807.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Sivan SS, Hayes AJ, Wachtel E, Caterson B, Merkher Y, Maroudas A, et al. Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc. Eur Spine J. 2014;23(Suppl 3):S344–53.

    Article  PubMed  Google Scholar 

  135. Skuntz S, Mankoo B, Nguyen MT, Hustert E, Nakayama A, Tournier-Lasserve E, et al. Lack of the mesodermal homeodomain protein MEOX1 disrupts sclerotome polarity and leads to a remodeling of the cranio-cervical joints of the axial skeleton. Dev Biol. 2009;332:383–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Smith TG, Sweetman D, Patterson M, Keyse SM, Münsterberg A. Feedback interactions between MKP3 and ERK MAP kinase control scleraxis expression and the specification of rib progenitors in the developing chick somite. Development. 2005;132:1305–14.

    Article  PubMed  CAS  Google Scholar 

  137. Smits P, Lefebvre V. Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and development of the nucleus pulposus of intervertebral discs. Development. 2003;130:1135–48.

    Article  PubMed  CAS  Google Scholar 

  138. Sosić D, Brand-Saberi B, Schmidt C, Christ B, Olson EN. Regulation of paraxis expression and somite formation by ectoderm- and neural tube-derived signals. Dev Biol. 1997;185:229–43.

    Article  PubMed  Google Scholar 

  139. Sparrow DB, Chapman G, Turnpenny PD. Dunwoodie SL disruption of the somitic molecular clock causes abnormal vertebral segmentation. Birth Defects Res C Embryo Today. 2007;81:93–110.

    Article  PubMed  CAS  Google Scholar 

  140. Spencer GS, Zorab PA. Spinal muscle in scoliosis. Part 1: histology and histochemistry. J Neurol Sci. 1976;30:127–42.

    Article  Google Scholar 

  141. Steinert AF, Kunz M, Prager P, Barthel T, Jakob F, Nöth U, et al. Mesenchymal stem cell characteristics of human anterior cruciate ligament outgrowth cells. Tissue Eng Part A. 2011;17:1375–88.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Summerbell D, Ashby PR, Coutelle O, Cox D, Yee S, Rigby PW. The expression of Myf5 in the developing mouse embryo is controlled by discrete and dispersed enhancers specific for particular populations of skeletal muscle precursors. Development. 2000;127:3745–57.

    PubMed  CAS  Google Scholar 

  143. Suzuki H, Ito Y, Shinohara M, Yamashita S, Ichinose S, Kishida A, et al. Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis. Proc Natl Acad Sci U S A. 2016;113:7840–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Swiatek PJ, Lindsell CE, del Amo FF, Weinmaster G, Gridley T. Notch1 is essential for postimplantation development in mice. Genes Dev. 1994;8:707–19.

    Article  PubMed  CAS  Google Scholar 

  145. Tajbakhsh S, Borello U, Vivarelli E, Kelly R, Papkoff J, Duprez D, et al. Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5. Development. 1998;125:4155–62.

    PubMed  CAS  Google Scholar 

  146. Takahashi Y, Sato Y. Somitogenesis as a model to study the formation of morphological boundaries and cell epithelialization. Develop Growth Differ. 2008;50:S149–55.

    Article  CAS  Google Scholar 

  147. Takahashi Y, Koizumi K, Takagi A, Kitajima S, Inoue T, Koseki H, et al. Mesp2 initiates somite segmentation through the Notch signalling pathway. Nat Genet. 2000;25:390–6.

    Article  PubMed  CAS  Google Scholar 

  148. Takahashi Y, Inoue T, Gossler A, Saga Y. Feedback loops comprising Dll1, Dll3 and Mesp2, and differential involvement of Psen1 are essential for rostrocaudal patterning of somites. Development. 2003;130:4259–68.

    Article  PubMed  CAS  Google Scholar 

  149. Takahashi Y, Takagi A, Hiraoka S, Koseki H, Kanno J, Rawls A, et al. Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation. Dev Dyn. 2007;236:1484–94.

    Article  PubMed  CAS  Google Scholar 

  150. Takimoto A, Mohri H, Kokubu C, Hiraki Y, Shukunami C. Pax1 acts as a negative regulator of chondrocyte maturation. Exp Cell Res. 2013;319:3128–39.

    Article  PubMed  CAS  Google Scholar 

  151. Tam PP, Trainor PA. Specification and segmentation of the paraxial mesoderm. Anat Embryol. 1994;189:275–305.

    Article  PubMed  CAS  Google Scholar 

  152. Tanaka M, Tickle C. Tbx18 and boundary formation in chick somite and wing development. Dev Biol. 2004;268:470–80.

    Article  PubMed  CAS  Google Scholar 

  153. Teboul L, Summerbell D, Rigby PW. The initial somitic phase of Myf5 expression requires neither Shh signaling nor Gli regulation. Genes Dev. 2003;17:2870–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Tonegawa A, Funayama N, Ueno N, Takahashi Y. Mesodermal subdivision along the mediolateral axis in chicken controlled by different concentrations of BMP-4. Development. 1997;124:1975–84.

    PubMed  CAS  Google Scholar 

  155. Tozer S, Duprez D. Tendon and ligament: development, repair and disease. Birth Defects Res C Embryo Today. 2005;75:226–36.

    Article  PubMed  CAS  Google Scholar 

  156. van den Akker E, Fromental-Ramain C, deGraaf W, LeMouellic H, Brulet P, Chambon P, Deschamps J. Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes. Development. 2001;128:1911–21.

    PubMed  Google Scholar 

  157. Veldhuizen AG, Wever DJ, Webb PJ. The aetiology of idiopathic scoliosis: biomechanical and neuromuscular factors. Eur Spine J. 2000;9:178–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Venters SJ, Thorsteinsdottir S, Duxson MJ. Early development of the myotome in the mouse. Dev Dyn. 1999;216:219–32.

    Article  PubMed  CAS  Google Scholar 

  159. Wagner J, Schmidt C, Nikowits W Jr, Christ B. Compartmentalization of the somite and myogenesis in chick embryos are influenced by wnt expression. Dev Biol. 2000;228:86–94.

    Article  PubMed  CAS  Google Scholar 

  160. Watanabe Y, Duprez D, Monsoro-Burq AH, Vincent C, Le Douarin NM. Two domains in vertebral development: antagonistic regulation by SHH and BMP4 proteins. Development. 1998;125:2631–9.

    PubMed  CAS  Google Scholar 

  161. Wellik DM. Hox patterning of the vertebrate axial skeleton. Dev Dyn. 2007;236:2454–63.

    Article  PubMed  CAS  Google Scholar 

  162. Wellik DM, Capecchi MR. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science. 2003;301:363–6.

    Article  PubMed  CAS  Google Scholar 

  163. Wood A, Thorogood P. Patterns of cell behavior underlying somitogenesis and notochord formation in intact vertebrate embryos. Dev Dyn. 1994;201:151–67.

    Article  PubMed  CAS  Google Scholar 

  164. Yang X, Arber S, William C, Li L, Tanabe Y, Jessell TM, Birchmeier C, Burden SJ. Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron. 2001;30:399–410.

    Article  PubMed  CAS  Google Scholar 

  165. Yarom R, Robin GC. Studies on spinal and peripheral muscles from patients with scoliosis. Spine. 1979;4:12–21.

    Article  PubMed  CAS  Google Scholar 

  166. Yasuhiko Y, Haraguchi S, Kitajima S, Takahashi Y, Kanno J, Saga Y. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression. Proc Natl Acad Sci U S A. 2006;103:3651–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Yoon ST, Su Kim K, Li J, Soo Park J, Akamaru T, Elmer WA, et al. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro. Spine. 2003;28:1773–80.

    Article  Google Scholar 

  168. Zetterberg C, Aniansson A, Grimby G. Morphology of the paravertebral muscles in adolescent idiopathic scoliosis. Spine. 1983;8:457–62.

    Article  PubMed  CAS  Google Scholar 

  169. Zuk T. The role of spinal and abdominal muscles in the pathogenesis of scoliosis. J Bone Joint Surg Br. 1962;44:102–5.

    Article  Google Scholar 

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Acknowledgments

We would like to thank Brent Adrian for preparing Figs. 1.1, 1.3, 1.4, 1.5, and 1.8.

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Authors and Affiliations

  1. School of Life Sciences, Arizona State University, Tempe, AZ, USA

    Alan Rawls & Rebecca E. Fisher

  2. Department of Basic Medical Sciences, The University of Arizona College of Medicine–Phoenix, Phoenix, AZ, USA

    Rebecca E. Fisher

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  1. School of Life Sciences, Arizona State University, Tempe, Arizona, USA

    Kenro Kusumi

  2. Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, Australia

    Sally L. Dunwoodie

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Rawls, A., Fisher, R.E. (2018). Developmental and Functional Anatomy of the Spine. In: Kusumi, K., Dunwoodie, S. (eds) The Genetics and Development of Scoliosis. Springer, Cham. https://doi.org/10.1007/978-3-319-90149-7_1

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