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Development 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 (IV) discs supported by robust spinal ligaments and muscles. All of these elements, bony, cartilaginous, ligamentous, and muscular, are essential to the structural integrity of the spine. The spine serves three vital functions: protecting the spinal cord and spinal nerves, transmitting the weight of the body, and providing a flexible axis for movements of the head and the torso. The vertebral column is capable of extension, flexion, lateral flexion (side to side), and rotation. However, the degree to which the spine is capable of these movements varies by region. These regions, including the cervical, the thoracic, the lumbar, and the sacrococcygeal spine, form four curvatures (Fig. 2.1). The thoracic and the sacrococcygeal curvatures are established in fetal development, while the cervical and the thoracic curvatures develop during infancy. The cervical curvature arises in response to holding the head upright, while the lumbar curvature develops as an infant begins to sit upright and walk. Congenital defects and degenerative diseases can result in exaggerated, abnormal curvatures. The most common of these include a thoracic kyphosis (or hunchback deformity), a lumbar lordosis (or swayback deformity), and scoliosis. Scoliosis involves a lateral curvature of greater than 10°, often accompanied by a rotational defect. To appreciate the potential underlying causes of scoliosis, we need to understand the cellular and genetic basis of vertebral column and skeletal muscle development from somites. In this chapter, we will review the embryonic development of the spine and associated muscles and link them to the functional anatomy of these structures in the adult.

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References

  • Afonin, B., Ho, M., Gustin, J.K., Meloty-Kapella, C., and Domingo, C.R. 2006. Cell behaviors associated with somite segmentation and rotation in Xenopus laevis. Dev Dyn. 235:3268–3279.

    Google Scholar 

  • Alexander, M.A. and Season, E.H. 1978. Idiopathic scoliosis: an electromyographic study. Arch. Phys. Med. Rehabil. 59:314–315.

    CAS  PubMed  Google Scholar 

  • Alvares, L.E., Schubert, F.R., Thorpe, C., Mootoosamy, R.C., Cheng, L., Parkyn, G., Lumsden, A., and Dietrich, S. 2003. Intrinsic, Hox-dependent cues determine the fate of skeletal muscle precursors. Dev. Cell 5:379–390.

    Article  CAS  PubMed  Google Scholar 

  • Aoyama, H. and Asamoto, K. 1988. Determination of somite cells: independence of cell differentiation and morphogenesis. Development. 104:15–28.

    Google Scholar 

  • Aoyama, H. and Asamoto, K. 2000. 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. 99:71–82.

    Article  CAS  PubMed  Google Scholar 

  • Arnold, H.H. and Braun, T. 2000. Genetics of muscle determination and development. Curr. Top. Dev. Biol. 48:129–164.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Baffi, M.O., Moran, M.A., and Serra, R. 2006. Tgfbr2 regulates the maintenance of boundaries in the axial skeleton. Dev. Biol. 296:363–374.

    Article  CAS  PubMed  Google Scholar 

  • Barrallo-Gimeno, A., and Nieto, M.A. 2005. The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132:3151–3161.

    Article  CAS  PubMed  Google Scholar 

  • Barrantes, I.B., Elia, A.J., Wünsch, K., Hrabe de Angelis, M.H., Mak, T.W., Rossant, J., Conlon, R.A., Gossler, A., and de la Pompa, J.L. 1999. Interaction between Notch signalling and Lunatic fringe during somite boundary formation in the mouse. Curr Biol. 9:470–480.

    Google Scholar 

  • Batlle, E., Sancho, E., Franci, C., Dominguez, D., Monfar, M., Baulida, J., and Garcia De Herreros, A. 2000. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol. 2:84–89.

    Article  CAS  PubMed  Google Scholar 

  • Berkes, C.A., Bergstrom, D.A., Penn, B.H., Seaver, K.J., Knoepfler, P.S., and Tapscott, S.J. 2004. Pbx marks genes for activation by MyoD indicating a role for a homeodomain protein in establishing myogenic potential. Mol. Cell 14:465–477.

    Article  CAS  PubMed  Google Scholar 

  • Borello, U., Berarducci, B., Murphy, P., Bajard, L., Buffa, V., Piccolo, S., Buckingham, M., and Cossu, G. 2006. The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis. Development 133:3723–3732.

    Article  CAS  PubMed  Google Scholar 

  • Borycki, A., Brown, A.M., and Emerson, C.P. Jr. 2000. Shh and Wnt signaling pathways converge to control Gli gene activation in avian somites. Development 127:2075–2087.

    CAS  PubMed  Google Scholar 

  • Borycki, A.G., Brunk, B., Tajbakhsh, S., Buckingham, M., Chiang, C., and Emerson, C.P. Jr. 1999. Sonic hedgehog controls epaxial muscle determination through Myf5 activation. Development 126:4053–4063.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Brent, A.E., Braun, T., and Tabin, C.J. 2005. Genetic analysis of interactions between the somitic muscle, cartilage and tendon cell lineages during mouse development. Development 132:515–528.

    Article  CAS  PubMed  Google Scholar 

  • Brent, A.E., Schweitzer, R., and Tabin, C.J. 2003. A somitic compartment of tendon progenitors. Cell 113:235–248.

    Article  CAS  PubMed  Google Scholar 

  • Brent, A.E. and Tabin, C.J. 2004. FGF acts directly on the somitic tendon progenitors through the Ets transcription factors Pea3 and Erm to regulate scleraxis expression. Development 131:3885–3896.

    Article  CAS  PubMed  Google Scholar 

  • Buchberger, A., Seidl, K., Klein, C., Eberhardt, H., and Arnold, H.H. 1998. cMeso-1, a novel bHLH transcription factor, is involved in somite formation in chicken embryos. Dev. Biol. 199:201–215.

    Article  CAS  PubMed  Google Scholar 

  • Burgess, R., Cserjesi, P., Ligon, K.L., and Olson, E.N. 1995. Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and developing somites. Dev. Biol. 168:296–306.

    Article  CAS  PubMed  Google Scholar 

  • Burgess, R., Rawls, A., Brown, D., Bradley, A., and Olson, E.N. 1996. Requirement of the paraxis gene for somite formation and musculoskeletal patterning. Nature 384:570–573.

    Article  CAS  PubMed  Google Scholar 

  • Butterworth, T.R. and James, C. 1969. Electromyographic studies in idiopathic scoliosis. South Med. J. 62:1008–1010.

    PubMed  Google Scholar 

  • Buxton, D.F. and Peck, D. 1989. Neuromuscular spindles relative to joint movement complexities. Clin. Anat. 2:211–224.

    Article  Google Scholar 

  • Bylund, P., Jansson, E., Dahlberg, E., and Eriksson, E. 1987. Muscle fiber types in thoracic erector spinae muscles. Clin. Orthop. 214:222–228.

    PubMed  Google Scholar 

  • Cailliet, R. 1988. Low Back Pain Syndrome. Fourth Edition. Philadelphia: FA Davis Company.

    Google Scholar 

  • Cano, A., Perez-Moreno, M.A., Rodrigo, I., Locascio, A., Blanco, M.J., del Barrio, M.G., Portillo, F., and Nieto, M.A. 2000. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol. 2:76–83.

    Article  CAS  PubMed  Google Scholar 

  • Capellini, T.D., Di Giacomo, G., Salsi, V., Brendolan, A., Ferretti, E., Srivastava, D., Zappavigna, V., and Selleri, L. 2006. Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression. Development 133:2263–2273.

    Article  CAS  PubMed  Google Scholar 

  • Capellini, T.D., Zewdu, R., Di Giacomo, G., Asciutti, S., Kugler, J.E., Di Gregorio, A., and Selleri, L. 2008. Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome. Dev. Biol. 321:500–514.

    Article  CAS  PubMed  Google Scholar 

  • Chan, Y.L., Cheng, J.C.Y., Guo, X., King, A.D., Griffith, J.F., and Metreweli, C. 1999. MRI evaluation of multifidus muscles in adolescent idiopathic scoliosis. Pediatr. Radiol. 29:360–363.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Condie, B.G. and Capecchi, M.R. 1994. Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions. Science 370:304–307.

    CAS  Google Scholar 

  • Conlon, R.A., Reaume, A.G., and Rossant, J. 1995. Notch1 is required for the coordinate segmentation of somites. Development. 121:1533–1545.

    Google Scholar 

  • Correia, K.M. and Conlon, R.A. 2000. Surface ectoderm is necessary for the morphogenesis of somites. Mech. Dev. 91:19–30.

    Article  CAS  PubMed  Google Scholar 

  • Cossu, G. and Borello, U. 1999. Wnt signaling and the activation of myogenesis in mammals. EMBO J. 18:6867–6872.

    Article  CAS  PubMed  Google Scholar 

  • Dale, J.K., Malapert, P., Chal, J., Vilhais-Neto, G., Maroto, M., Johnson, T., Jayasinghe, S., Trainor, P., Herrmann, B., and Pourquié, O. 2006. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Dev. Cell 10:355–366.

    Article  CAS  PubMed  Google Scholar 

  • de la Pompa, J.L., Wakeham, A., Correia, K.M., Samper, E., Brown, S., Aguilera, R.J., Nakano, T., Honjo, T., Mak, T.W., Rossant, J., and Conlon, R.A. 1997. Conservation of the Notch signalling pathway in mammalian neurogenesis. Development 124:1139–1148.

    PubMed  Google Scholar 

  • Denetclaw, W.F. Jr., Christ, B., and Ordahl, C.P. 1997. Location and growth of epaxial myotome precursor cells. Development 124:1601–1610.

    CAS  PubMed  Google Scholar 

  • Denetclaw, W.F. and Ordahl, C.P. 2000. The growth of the dermomyotome and formation of early myotome lineages in thoracolumbar somites of chicken embryos. Development 127: 893–905.

    CAS  PubMed  Google Scholar 

  • Dockter, J.L. 2000. Sclerotome induction and differentiation. Curr. Top. Dev. Biol. 48:77–127.

    Article  CAS  PubMed  Google Scholar 

  • Duband, J.L., Dufour, S., Hatta, K., Takeichi, M., Edelman, G.M., and Thiery, J.P. 1987. Adhesion molecules during somitogenesis in the avian embryo. J. Cell Biol. 104:1361–1374.

    Article  CAS  PubMed  Google Scholar 

  • Dubrulle, J., and Pourquié, O. 2004. Coupling segmentation to axis formation. Development 131:5783–5793.

    Article  CAS  PubMed  Google Scholar 

  • Dunwoodie, S.L., Clements, M., Sparrow, D.B., Sa, X., Conlon, R.A., and Beddington, R.S. 2002. Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm. Development 129:1795–1806.

    Google Scholar 

  • Fan, C.M., and Tessier-Lavigne, M. 1994. Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog. Cell 79: 1175–1186.

    Article  CAS  PubMed  Google Scholar 

  • Fidler, M.W. and Jowett, R.L. 1976. Muscle imbalance in the aetiology of scoliosis. J. Bone Joint Surg. 58-B:200–201.

    Google Scholar 

  • Ford, D.M., Bagnall, K.M., McFadden, K.D., Greenhill, B.J., and Raso, V.J. 1984. Paraspinal muscle imbalance in adolescent idiopathic scoliosis. Spine 9:373–376.

    Article  CAS  PubMed  Google Scholar 

  • Furumoto, T.A., Miura, N., Akasaka, T., Mizutanikoseki, Y., Sudo, H., Fukuda, K., Maekawa, M., Yuasa, S., Fu, Y., Moriya, H., Taniguchi, M., Imai, K., Dahl, E., Balling, R., Pavlova, M., Gossler, A., and Koseki, H. 1999. Notochord-dependent expression of MFH1 and PAX1 cooperates maintain the proliferation of sclerotome cells during the vertebral column development. Dev. Biol. 210:15–29.

    Article  CAS  PubMed  Google Scholar 

  • Geetha-Loganathan, P., Nimmagadda, S., Huang, R., Christ, B., and Scaal, M. 2006. Regulation of ectodermal Wnt6 expression by the neural tube is transduced by dermomyotomal Wnt11: a mechanism of dermomyotomal lip sustainment. Development 133:2897–2904.

    Article  CAS  PubMed  Google Scholar 

  • Goldstein, R.S. and Kalcheim, C. 1992. Determination of epithelial half-somites in skeletal morphogenesis. Development 116:441–445.

    CAS  PubMed  Google Scholar 

  • Henry, C.A., Hall, L.A., Burr Hille, M., Solnica-Krezel, L., and Cooper, M.S. 2000. Somites in zebrafish doubly mutant for knypek and trilobite form without internal mesenchymal cells or compaction. Curr. Biol. 10:1063–1066.

    Article  CAS  PubMed  Google Scholar 

  • Horikawa, K., Radice, G., Takeichi, M., and Chisaka, O. 1999. Adhesive subdivisions intrinsic to the epithelial somites. Dev. Biol. 215:182–189.

    Article  CAS  PubMed  Google Scholar 

  • Hrabĕ de Angelis, M., McIntyre, J., 2nd, and Gossler, A. 1997. Maintenance of somite borders in mice requires the Delta homologue DII1. Nature 386:717–721.

    Article  PubMed  Google Scholar 

  • Huang, R., Zhi, Q., Neubuser, A., Muller, T.S., Brand-Saberi, B., Christ, B., and Wilting, J. 1996. Function of somite and somitocoele cells in the formation of the vertebral motion segment in avian embryos. Acta Anat. (Basel) 155:231–241.

    Article  CAS  Google Scholar 

  • Jacob, H.J. and Christ, B. 1980. On the formation of muscular pattern in the chick limb. In Teratology of the Limbs. pp. 89–97. Berlin: Walter de Gruyter and Co.

    Google Scholar 

  • Jiang, Y.J., Aerne, B.L., Smithers, L., Haddon, C., Ish-Horowicz, D., and Lewis, J. 2000. Notch signaling and the synchronization of the somite segmentation clock. Nature 408:475–479.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, J., Rhee, J., Parsons, S.M., Brown, D., Olson, E.N., and Rawls, A. 2001. The anterior/posterior polarity of somites is disrupted in paraxis-deficient mice. Dev. Biol. 229:176–187.

    Article  CAS  PubMed  Google Scholar 

  • Kahane, N., Cinnamon, Y., and Kalcheim, C. 1998. The cellular mechanism by which the dermomyotome contributes to the second wave of myotome development. Development 125:4259–4271.

    CAS  PubMed  Google Scholar 

  • Kardon, G., Harfe, B.D., and Tabin, C.T. 2003. A Tcf4-positive mesodermal population provides a prepattern for vertebrate limb muscle patterning. Dev. Cell 5:937–944.

    Article  CAS  PubMed  Google Scholar 

  • Keynes, R.J. and Stern, C.D. 1988. Mechanisms of vertebrate segmentation. Development 103:413–429.

    CAS  PubMed  Google Scholar 

  • Khosla, S., Tredwell, S.J., Day, B., Shinn, S.L., and Ovalle, W.K. 1980. An ultrastructural study of multifidus muscle in progressive idiopathic scoliosis-changes resulting from a sarcolemmal defect of the myotendinous junction. J. Neurol. Sci. 46:13–31.

    Article  CAS  PubMed  Google Scholar 

  • Kim, D.J., Moon, S.H., Kim, H., Kwon, U.H., Park, M.S., Han, K.J., Hahn, S.B., and Lee, H.M. 2003. Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells. Spine 28:2679–2684.

    Google Scholar 

  • Kim, S.Y., Paylor, S.W., Magnuson, T., and Schumacher, A. 2006. Juxtaposed Polycomb complexes co-regulate vertebral identity. Development 133:4957–4968.

    Article  CAS  PubMed  Google Scholar 

  • Koizumi, K., Nakajima, M., Yuasa, S., Saga, Y., Sakai, T., Kuriyama, T., Shirasawa, T., and Koseki, H. 2001. The role of presenilin 1 during somite segmentation. Development 128: 1391–1402.

    CAS  PubMed  Google Scholar 

  • Kulesa, P.M. and Fraser, S.E. 2002. Cell dynamics during somite boundary formation revealed by time-lapse analysis. Science 298:991–995.

    Article  CAS  PubMed  Google Scholar 

  • Kulesa, P.M., Schnell, S., Rudloff, S., Baker, R.E., and Maini, P.K. 2007. From segment to somite: segmentation epithelialization analyzed within quantitative frameworks. Dev. Dyn. 236:1392–1402.

    Article  CAS  PubMed  Google Scholar 

  • Kusumi, K., Sun, E.S., Kerrebrock, A.W., Bronson, R.T., Chi, D.C., Bulotsky, M.S., Spencer, J.B., Birren, B.W., Frankel, W.N., and Lander, E.S. 1998. The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries. Nat. Genet. 19(3):274–278.

    Article  CAS  PubMed  Google Scholar 

  • Lewis, E.B. 1978. A gene complex controlling segmentation in Drosophila. Nature 276:565–570.

    Article  CAS  PubMed  Google Scholar 

  • Li, J., Yoon, S.T., and Hutton, W.C. 2004. 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. 17:423–428.

    Article  PubMed  Google Scholar 

  • Linker, C., Lesbros, C., Gros, J., Burrus, L.W., Rawls, A., and Marcelle, C. 2005. Beta-Catenin-dependent Wnt signalling controls the epithelial organisation of somites through the activation of paraxis. Development 132:3895–3905.

    Article  CAS  PubMed  Google Scholar 

  • Mackie, E.J., Ahmed, Y.A., Tatarczuch, L., Chen, K.S., and Mirams, M. 2008. Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int. J. Biochem. Cell Biol. 40:46–62.

    Article  CAS  PubMed  Google Scholar 

  • Maconochie, M.K., Nonchev, S., Studer, M., Chan, S.K., Popperl, H., Sham, M.H., Mann, R.S., and Krumlauf, R. 1997. Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1. Genes Dev. 11:1885–1895.

    Article  CAS  PubMed  Google Scholar 

  • Mankoo, B.S., Skuntz, S., Harrigan, I., Grigorieva, E., Candia, A., Wright, C.V., Arnheiter, H., and Pachnis, V. 2003. The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites. Development 130:4655–4664.

    Article  CAS  PubMed  Google Scholar 

  • Mannion, A.F., Meier, M., Grob, D., and Müntener, M. 1998. Paraspinal muscle fibre type alterations associated with scoliosis: an old problem revisited with new evidence. Eur. Spine J. 7:289–293.

    Article  CAS  PubMed  Google Scholar 

  • McDermott, A., Gustafsson, M., Elsam, T., Hui, C.C., Emerson, C.P. Jr., and Borycki, A.G. 2005. Gli2 and Gli3 have redundant and context-dependent function in skeletal muscle formation. Development 132:345–357.

    Article  CAS  PubMed  Google Scholar 

  • McIntyre, D.M., Rakshit, S., Yallowitz, A.R., Loken, L., Jeannotte, L., Capecchi, M.R., and Wellik, D.M. 2007. Hox Patterning of the vertebrate rib cage. Development 134: 2981–2989.

    Article  CAS  PubMed  Google Scholar 

  • McKinsey, T.A., Zhang, C.L., Lu, J., and Olson, E.N. 2000. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 408:106–111.

    Article  CAS  PubMed  Google Scholar 

  • McKinsey, T.A., Zhang, C.L., and Olson, E.N. 2001. Control of muscle development by dueling HATs and HDACs. Curr. Opin. Genet. Dev. 11:497–504.

    Article  CAS  PubMed  Google Scholar 

  • McMahon, J.A., Takada, S., Zimmerman, L.B., and McMhaon, A.P. 1998. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev. 12:1438–1452.

    Article  CAS  PubMed  Google Scholar 

  • Meier, M.P., Klein, M.P., Krebs, D., Grob, D., and Müntener, M. 1997. Fiber transformations in multifidus muscle of young patients with idiopathic scoliosis. Spine 22:2357–2364.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Moens, C.B. and Selleri, L. 2006. Hox cofactors in vertebrate development. Dev. Biol. 291:193–206.

    Article  CAS  PubMed  Google Scholar 

  • Molkentin, J.D. and Olson, E.N. 1996. Defining the regulatory networks for muscle development. Curr. Opin. Genet. Dev. 6:445–453.

    Article  CAS  PubMed  Google Scholar 

  • Monsoro-Burq, A.H., Bontoux, M., Teillet, M.A., and Le Douarin, N.M. 1994. Heterogeneity in the development of the vertebra. Proc. Natl. Acad. Sci. U.S.A. 91:10435–10439.

    Article  CAS  PubMed  Google Scholar 

  • Monsoro-Burq, A.H., Duprez, D., Watanabe, Y., Bontoux, M., Vincent, C., Brickell, P., and Le Douarin, N. 1996. The role of bone morphogenetic proteins in vertebral development. Development 122:3607–3616.

    CAS  PubMed  Google Scholar 

  • Moore, K.L. and Dalley, A.F. 2006. Clinically Oriented Anatomy. Baltimore: Lippincott Williams and Wilkins.

    Google Scholar 

  • Morimoto, M., Sasaki, N., Oginuma, M., Kiso, M., Igarashi, K., Aizaki, K., Kanno, J., and Saga, Y. 2007. The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite. Development 134:1561–1569.

    Article  CAS  PubMed  Google Scholar 

  • Nakaya, Y., Kuroda, S., Katagiri, Y.T., Kaibuchi, K., and Takahashi, Y. 2004. Mesenchymal-epithelial transition during somitic segmentation is regulated by differential roles of Cdc42 and Rac1. Dev. Cell 7:425–438.

    Article  CAS  PubMed  Google Scholar 

  • Oka, C., Nakano, T., Wakeham, A., de la Pompa, J.L., Mori, C., Sakai, T., Okazaki, S., Kawaichi, M., Shiota, K., Mak, T.W., and Honjo, T. 1995. Disruption of the mouse RBP-J kappa gene results in early embryonic death. Development 121:3291–3301.

    CAS  PubMed  Google Scholar 

  • Ordahl, C.P., Berdougo, E., Venters, S.J., and Denetclaw, W.F. Jr. 2001. The dermomyotome dorsomedial lip drives growth and morphogenesis of both the primary myotome and dermomyotome epithelium. Development 128:1731–1744.

    CAS  PubMed  Google Scholar 

  • Ordahl, C.P. and Le Douarin, N.M. 1992. Two myogenic lineages within the developing somite. Development 114:339–353.

    CAS  PubMed  Google Scholar 

  • Paavola, L.G., Wilson, D.B., and Center, E.M. 1980. Histochemistry of the developing notochord, perichordal sheath and vertebrae in Danforth’s short-tail (sd) and normal C57BL/6 mice. J. Embryol. Exp. Morphol. 55:227–245.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Peters, H., Wilm, B., Sakai, N., Imai, K., Maas, R., and Balling, R. 1999. Pax1 and Pax9 synergistically regulate vertebral column development. Development 126:5399–5408.

    CAS  PubMed  Google Scholar 

  • Popperl, H., Bienz, M., Studer, M., Chan, S.K., Aparicio, S., Brenner, S., Mann, R.S., and Krumlauf, R. 1995. Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell 81:1031–1042.

    Article  CAS  PubMed  Google Scholar 

  • Pourquie, O., Coltey, M., Teillet, M.A., Ordahl, C., and Le Douarin, M. 1993. Control of dorsoventral patterning of somitic derivatives by notochord and floor plate. Proc. Natl. Acad. Sci. U.S.A. 90:5242–5246.

    Article  CAS  PubMed  Google Scholar 

  • Puri, P.L., Sartorelli, V., Yang, X.J., Hamamori, Y., Ogryzko, V.V., Howard, B.H., Kedes, L., Wang, J.Y., Graessmann, A., Nakatani, Y., and Levrero, M. 1997. Differential roles of p300 and PCAF acetyltransferases in muscle differentiation. Mol. Cell 1:35–45.

    Article  CAS  PubMed  Google Scholar 

  • Radice, G.L., Rayburn, H., Matsunami, H., Knudsen, K.A., Takeichi, M., and Hynes, R.O. 1997. Developmental defects in mouse embryos lacking N-cadherin. Dev. Biol. 181:64–78.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Reuber, M., Schultz, A., McNeill, T., and Spencer, D. 1983. Trunk muscle myoelectric activities in idiopathic scoliosis. Spine 8:447–456.

    Article  CAS  PubMed  Google Scholar 

  • Saga, Y., Hata, N., Koseki, H., and Taketo, M.M. 1997. Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation. Genes Dev. 11:1827–1839.

    Article  CAS  PubMed  Google Scholar 

  • Sahgal, V., Shah, A., Flanagan, N., Schaffer, M., Kane, W., Subramani, V., and Singh, H. 1983. Morphologic and morphometric studies of muscle in idiopathic scoliosis. Acta Orthop. 54:242–251.

    Article  CAS  Google Scholar 

  • Sartorelli, V., Puri, P.L., Hamamori, Y., Ogryzko, V., Chung, G., Nakatani, Y., Wang, J.Y., and Kedes, L. 1999. Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program. Mol. Cell 4:725–734.

    Article  CAS  PubMed  Google Scholar 

  • Sato, Y. and Takahashi, Y. 2005. A novel signal induces a segmentation fissure by acting in a ventral-to-dorsal direction in the presomitic mesoderm. Dev. Biol. 282:183–191.

    Article  CAS  PubMed  Google Scholar 

  • Sato, Y., Yasuda, K., and Takahashi, Y. 2002. Morphological boundary forms by a novel inductive event mediated by Lunatic fringe and Notch during somitic segmentation. Development 129:3633–3644.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Schubert, F.R., Tremblay, P., Mansouri, A., Faisst, A.M., Kammandel, B., Lumsden, A., Gruss, P., and Dietrich, S. 2001. Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites. Dev. Dyn. 222:506–521.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Skuntz, S., Mankoo, B., Nguyen, M.T., Hustert, E., Nakayama, A., Tournier-Lasserve, E., Wright, C.V., Pachnis, V., Bharti, K., and Arnheiter, H. 2009. 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 Aug 15;332(2):383–95.

    Google Scholar 

  • Smith, T.G., Sweetman, D., Patterson, M., Keyse, S.M., and Münsterberg, A. 2005. Feedback interactions between MKP3 and ERK MAP kinase control scleraxis expression and the specification of rib progenitors in the developing chick somite. Development 132: 1305–1314.

    Article  CAS  PubMed  Google Scholar 

  • Smits, P. and Lefebvre, V. 2003. Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and development of the nucleus pulposus of intervertebral discs. Development 130:1135–1148.

    Article  CAS  PubMed  Google Scholar 

  • Sosić, D., Brand-Saberi, B., Schmidt, C., Christ, B., and Olson, E.N. 1997. Regulation of paraxis expression and somite formation by ectoderm- and neural tube-derived signals. Dev. Biol. 185:229–243.

    Article  PubMed  Google Scholar 

  • Sparrow, D.B., Chapman, G., Turnpenny, P.D., and Dunwoodie, S.L. 2007. Disruption of the somitic molecular clock causes abnormal vertebral segmentation. Birth Defects Res. C Embryo Today 81:93–110.

    Article  CAS  PubMed  Google Scholar 

  • Spencer, G.S. and Zorab, P.A. 1976. Spinal muscle in scoliosis. Part 1: histology and histochemistry. J. Neurol. Sci. 30:127–142.

    Google Scholar 

  • Summerbell, D., Ashby, P.R., Coutelle, O., Cox, D., Yee, S., and Rigby, P.W. 2000. 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 127:3745–3757.

    CAS  PubMed  Google Scholar 

  • Swiatek, P.J., Lindsell, C.E., del Amo, F.F., Weinmaster, G., and Gridley, T. 1994. Notch1 is essential for postimplantation development in mice. Genes Dev. 8:707–719.

    Article  CAS  PubMed  Google Scholar 

  • Tajbakhsh, S., Borello, U., Vivarelli, E., Kelly, R., Papkoff, J., Duprez, D., Buckingham, M., and Cossu, G. 1998. 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 125:4155–4162.

    CAS  PubMed  Google Scholar 

  • Takahashi, Y., Inoue, T., Gossler, A., and Saga, Y. 2003. Feedback loops comprising Dll1, Dll3 and Mesp2, and differential involvement of Psen1 are essential for rostrocaudal patterning of somites. Development 130:4259–4268.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi, Y., Koizumi, K., Takagi, A., Kitajima, S., Inoue, T., Koseki, H., and Saga, Y. 2000. Mesp2 initiates somite segmentation through the Notch signalling pathway. Nat. Genet. 25:390–396.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi, Y. and Sato, Y. 2008. Somitogenesis as a model to study the formation of morphological boundaries and cell epithelialization. Develop. Growth Differ. 50:S149–S155.

    Article  CAS  Google Scholar 

  • Takahashi, Y., Takagi, A., Hiraoka, S., Koseki, H., Kanno, J., Rawls, A., and Saga, Y. 2007. Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation. Dev. Dyn. 236:1484–1494.

    Article  CAS  PubMed  Google Scholar 

  • Tam, P.P. and Trainor, P.A. 1994. Specification and segmentation of the paraxial mesoderm. Anat. Embryol. 189:275–305.

    Article  CAS  PubMed  Google Scholar 

  • Tanaka, M. and Tickle, C. 2004. Tbx18 and boundary formation in chick somite and wing development. Dev. Biol. 268:470–480.

    Article  CAS  PubMed  Google Scholar 

  • Teboul, L., Summerbell, D., and Rigby, P.W. 2003. The initial somitic phase of Myf5 expression requires neither Shh signaling nor Gli regulation. Genes Dev. 17:2870–2874.

    Article  CAS  PubMed  Google Scholar 

  • Teppner, I., Becker, S., de Angelis, M.H., Gossler, A., and Beckers, J. 2007. Compartmentalised expression of Delta-like 1 in epithelial somites is required for the formation of intervertebral joints. BMC Dev. Biol. 7:68.

    Article  PubMed  CAS  Google Scholar 

  • Tonegawa, A., Funayama, N., Ueno, N., and Takahashi, Y. 1997. Mesodermal subdivision along the mediolateral axis in chicken controlled by different concentrations of BMP-4. Development 124:1975–1984.

    CAS  PubMed  Google Scholar 

  • Tozer, S. and Duprez, D. 2005. Tendon and ligament: development, repair and disease. Birth Defects Res. C Embryo Today 75:226–236.

    Article  CAS  PubMed  Google Scholar 

  • van den Akker, E., Fromental-Ramain, C., deGraaf, W., LeMouellic, H., Brulet, P., Chambon, P., and Deschamps, J. 2001. Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes. Development 128:1911–1921.

    PubMed  Google Scholar 

  • Venters, S.J., Thorsteinsdottir, S., and Duxson, M.J. 1999. Early development of the myotome in the mouse. Dev. Dyn. 216:219–232.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Watanabe, Y., Duprez, D., Monsoro-Burq, A.H., Vincent, C., and Le Douarin, N.M. 1998. Two domains in vertebral development: antagonistic regulation by SHH and BMP4 proteins. Development 125:2631–2639.

    CAS  PubMed  Google Scholar 

  • Wellik, D.M. 2007. Hox patterning of the vertebrate axial skeleton. Dev. Dyn. 236:2454–2463.

    Article  CAS  PubMed  Google Scholar 

  • Wellik, D.M. and Capecchi, M.R. 2003. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science 301:363–366.

    Article  CAS  PubMed  Google Scholar 

  • Wood, A. and Thorogood, P. 1994. Patterns of cell behavior underlying somitogenesis and notochord formation in intact vertebrate embryos. Dev. Dyn. 201:151–167.

    CAS  PubMed  Google Scholar 

  • Yang, X., Arber, S., William, C., Li, L., Tanabe, Y., Jessell, T.M., Birchmeier, C., and Burden, S.J. 2001. Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron 30:399–410.

    Article  CAS  PubMed  Google Scholar 

  • Yarom, R. and Robin, G.C. 1979. Studies on spinal and peripheral muscles from patients with scoliosis. Spine 4:12–21.

    Article  CAS  PubMed  Google Scholar 

  • Yasuhiko, Y., Haraguchi, S., Kitajima, S., Takahashi, Y., Kanno, J., and Saga, Y. 2006. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression. Proc. Natl. Acad. Sci. U.S.A. 103:3651–3656.

    Article  CAS  PubMed  Google Scholar 

  • Yoon, S.T., Su Kim, K., Li, J., Soo Park, J., Akamaru, T., Elmer, W.A., and Hutton, W.C. 2003. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro. Spine 28: 1773–1780.

    Article  Google Scholar 

  • Zetterberg, C., Aniansson, A., and Grimby, G. 1983. Morphology of the paravertebral muscles in adolescent idiopathic scoliosis. Spine 8:457–462.

    Article  CAS  PubMed  Google Scholar 

  • Zuk, T. 1962. The role of spinal and abdominal muscles in the pathogenesis of scoliosis. J. Bone Joint Surg. Br. 44:102–105.

    Google Scholar 

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Acknowledgments

We would like to thank Brent Adrian for preparing Figs. 2.1, 2.3, 2.4, 2.5, and 2.8.

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Rawls, A., Fisher, R.E. (2010). Development and Functional Anatomy of the Spine. In: Kusumi, K., Dunwoodie, S. (eds) The Genetics and Development of Scoliosis. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1406-4_2

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