Skip to main content

Development of the Intervertebral Disc

  • Chapter
  • First Online:
The Intervertebral Disc

Abstract

Intervertebral discs are derived from embryonic structures called the sclerotome and notochord (Paavola et al. 1980; Theiler 1988; Rufai et al. 1995). The nucleus pulposus, the cushioning core of the mature intervertebral disc, is derived from the notochord, while the annulus fibrosus, which provides the structural properties of the disc, is derived from sclerotome (Christ et al. 2004, 2007; Christ and Scaal 2008). The sclerotome is derived from the somites, transient structures that determine the segmented nature of the embryo. In response to signals from the notochord and floor plate of the neural tube, the maturing somites undergo dorsal-ventral compartmentalization establishing the dermomyotome and sclerotome, the latter forming most of the connective tissues of the future axial skeleton. The development of the sclerotome is characterized by proliferation and expansion of cells as well as the formation of three subcompartments: ventral, lateral, and dorsal. The ventral sclerotome gives rise to the vertebral bodies and annulus fibrosus and is made up of Pax-1-expressing cells that have invaded the perinotochordal space (Monsoro-Burq et al. 1994; Peters et al. 1999).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams DS, Keller R, Koehl MA (1990) The mechanics of notochord elongation, straightening and stiffening in the embryo of Xenopus laevis. Development 110(1):115–130

    PubMed  CAS  Google Scholar 

  • Alexander PG, Tuan RS (2010) Role of environmental factors in axial skeletal dysmorphogenesis. Birth Defects Res C Embryo Today 90(2):118–132

    Article  PubMed  CAS  Google Scholar 

  • Ando T, Semba K, Suda H, Sei A, Mizuta H, Araki M, Abe K, Imai K, Nakagata N, Araki K, Yamamura K (2011) The floor plate is sufficient for development of the sclerotome and spine without the notochord. Mech Dev 128(1–2):129–140

    Article  PubMed  CAS  Google Scholar 

  • Asai-Coakwell M, French CR, Ye M, Garcha K, Bigot K, Perera AG, Staehling-Hampton K, Mema SC, Chanda B, Mushegian A, Bamforth S, Doschak MR, Li G, Dobbs MB, Giampietro PF, Brooks BP, Vijayalakshmi P, Sauve Y, Abitbol M, Sundaresan P, van Heyningen V, Pourquie O, Underhill TM, Waskiewicz AJ, Lehmann OJ (2009) Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Hum Mol Genet 18(6):1110–1121

    Article  PubMed  CAS  Google Scholar 

  • Aszódi A, Chan D, Hunziker E, Bateman JF, Fässler R (1998) Collagen II is essential for the removal of the notochord and the formation of intervertebral discs. J Cell Biol 143(5):1399–1412

    Article  PubMed  Google Scholar 

  • Aulehla A, Pourquié O (2010) Signaling gradients during paraxial mesoderm development. Cold Spring Harb Perspect Biol 2(2)

    Google Scholar 

  • Aulehla A, Wehrle C, Brand-Saberi B, Kemler R, Gossler A, Kanzler B, Herrmann BG (2003) Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev Cell 4(3):395–406

    Article  PubMed  CAS  Google Scholar 

  • Aulehla A, Wiegraebe W, Baubet V, Wahl MB, Deng C, Taketo M, Lewandoski M, Pourquie O (2008) A [beta]-catenin gradient links the clock and wavefront systems in mouse embryo segmentation. Nat Cell Biol 10(2):186–193

    Article  PubMed  CAS  Google Scholar 

  • Baffi MO, Slattery E, Sohn P, Moses HL, Chytil A, Serra R (2004) Conditional deletion of the TGF-beta type II receptor in Col2a expressing cells results in defects in the axial skeleton without alterations in chondrocyte differentiation or embryonic development of long bones. Dev Biol 276(1):124–142

    Article  PubMed  CAS  Google Scholar 

  • Baffi MO, Moran MA, Serra R (2006) Tgfbr2 regulates the maintenance of boundaries in the axial skeleton. Dev Biol 296(2):363–374

    Article  PubMed  CAS  Google Scholar 

  • Bagnall KM (1992) The migration and distribution of somite cells after labelling with the carbocyanine dye, Dil: the relationship of this distribution to segmentation in the vertebrate body. Anat Embryol (Berl) 185(4):317–324

    Article  CAS  Google Scholar 

  • Bagnall KM, Sanders EJ (1989) The binding pattern of peanut lectin associated with sclerotome migration and the formation of the vertebral axis in the chick embryo. Anat Embryol (Berl) 180(5):505–513

    Article  CAS  Google Scholar 

  • Bagnall KM, Higgins SJ, Sanders EJ (1988) The contribution made by a single somite to the vertebral column: experimental evidence in support of resegmentation using the chick-quail chimaera model. Development 103(1):69–85

    PubMed  CAS  Google Scholar 

  • Barrios A, Poole RJ, Durbin L, Brennan C, Holder N, Wilson SW (2003) Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis. Curr Biol 13(18):1571–1582

    Article  PubMed  CAS  Google Scholar 

  • Bellairs R, Curtis AS, Sanders EJ (1978) Cell adhesiveness and embryonic differentiation. J Embryol Exp Morphol 46:207–213

    PubMed  CAS  Google Scholar 

  • Bessho Y, Hirata H, Masamizu Y, Kageyama R (2003) Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock. Genes Dev 17(12):1451–1456

    Article  PubMed  CAS  Google Scholar 

  • Bettenhausen B, Hrabe de Angelis M, Simon D, Guenet JL, Gossler A (1995) Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta. Development 121(8):2407–2418

    PubMed  CAS  Google Scholar 

  • Birk DE, Trelstad RL (1986) Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation. J Cell Biol 103(1):231–240

    Article  PubMed  CAS  Google Scholar 

  • Borycki AG, Mendham L, Emerson CP (1998) Control of somite patterning by Sonic hedgehog and its downstream signal response genes. Development 125(4):777–790

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Brand-Saberi B, Rudloff S, Gamel AJ (2008) Avian somitogenesis: translating time and space into pattern. Adv Exp Med Biol 638:42–57

    Article  PubMed  Google Scholar 

  • Brend T, Holley SA (2009) Balancing segmentation and laterality during vertebrate development. Semin Cell Dev Biol 20(4):472–478

    Article  PubMed  Google Scholar 

  • Brent AE (2005) Somite formation: where left meets right. Curr Biol 15(12):R468–R470

    Article  PubMed  CAS  Google Scholar 

  • Brent AE, Schweitzer R, Tabin CJ (2003) A somitic compartment of tendon progenitors. Cell 113(2):235–248

    Article  PubMed  CAS  Google Scholar 

  • Brent AE, Braun T, Tabin CJ (2005) Genetic analysis of interactions between the somitic muscle, cartilage and tendon cell lineages during mouse development. Development 132(3):515–528

    Article  PubMed  CAS  Google Scholar 

  • Bruggeman BJ, Maier JA, Mohiuddin YS, Powers R, Lo Y, Guimaraes-Camboa N, Evans SM, Harfe BD (2012) Avian intervertebral disc arises from rostral sclerotome and lacks a nucleus pulposus: implications for evolution of the vertebrate disc. Dev Dyn 241(4):675–683

    Article  PubMed  CAS  Google Scholar 

  • Burgess R, Rawls A, Brown D, Bradley A, Olson EN (1996) Requirement of the paraxis gene for somite formation and musculoskeletal patterning. Nature 384(6609):570–573

    Article  PubMed  CAS  Google Scholar 

  • Burke AC, Nelson CE, Morgan BA, Tabin C (1995) Hox genes and the evolution of vertebrate axial morphology. Development 121(2):333–346

    PubMed  CAS  Google Scholar 

  • Candia AF, Watabe T, Hawley SH, Onichtchouk D, Zhang Y, Derynck R, Niehrs C, Cho KW (1997) Cellular interpretation of multiple TGF-beta signals: intracellular antagonism between activin/BVg1 and BMP-2/4 signaling mediated by Smads. Development 124(22):4467–4480

    PubMed  CAS  Google Scholar 

  • Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383(6599):407–413

    Article  PubMed  CAS  Google Scholar 

  • Choi K-S, Harfe BD (2011) Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs. Proc Natl Acad Sci 108(23):9484–9489

    Article  PubMed  CAS  Google Scholar 

  • Choi KS, Cohn MJ, Harfe BD (2008) Identification of nucleus pulposus precursor cells and notochordal remnants in the mouse: implications for disk degeneration and chordoma formation. Dev Dyn 237(12):3953–3958

    Article  PubMed  CAS  Google Scholar 

  • Christ B, Ordahl CP (1995) Early stages of chick somite development. Anat Embryol (Berl) 191(5):381–396

    Article  CAS  Google Scholar 

  • Christ B, Scaal M (2008) Formation and differentiation of avian somite derivatives. Adv Exp Med Biol 638:1–41

    Article  PubMed  Google Scholar 

  • Christ B, Huang R, Wilting J (2000) The development of the avian vertebral column. Anat Embryol (Berl) 202(3):179–194

    Article  CAS  Google Scholar 

  • Christ B, Huang R, Scaal M (2004) Formation and differentiation of the avian sclerotome. Anat Embryol (Berl) 208(5):333–350

    Article  Google Scholar 

  • Christ B, Huang R, Scaal M (2007) Amniote somite derivatives. Dev Dyn 236(9):2382–2396

    Article  PubMed  CAS  Google Scholar 

  • Clarke RA, Singh S, Mckenzie H, Kearsley JH, Yip MY (1995) Familial Klippel-Feil syndrome and paracentric inversion Inv(8)(Q22.2q23.3). Am J Hum Genet 57(6):1364–1370

    PubMed  CAS  Google Scholar 

  • Colbjorn Larsen K, Fuchtbauer EM, Brand-Saberi B (2006) The neural tube is required to maintain primary segmentation in the sclerotome. Cells Tissues Organs 182(1):12–21

    Article  PubMed  Google Scholar 

  • Conlon RA, Reaume AG, Rossant J (1995) Notch1 is required for the coordinate segmentation of somites. Development 121(5):1533–1545

    PubMed  CAS  Google Scholar 

  • Cooke J, Zeeman EC (1976) A clock and wavefront model for control of the number of repeated structures during animal morphogenesis. J Theor Biol 58(2):455–476

    Article  PubMed  CAS  Google Scholar 

  • Couly GF, Coltey PM, Le Douarin NM (1993) The triple origin of skull in higher vertebrates: a study in quail-chick chimeras. Development 117(2):409–429

    PubMed  CAS  Google Scholar 

  • Crossin KL, Hoffman S, Grumet M, Thiery JP, Edelman GM (1986) Site-restricted expression of cytotactin during development of the chicken embryo. J Cell Biol 102(5):1917–1930

    Article  PubMed  CAS  Google Scholar 

  • Dahia CL, Mahoney EJ, Durrani AA, Wylie C (2009) Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging. Spine (Phila Pa 1976) 34(5):456–462

    Article  Google Scholar 

  • Dale RM, Topczewski J (2011) Identification of an evolutionarily conserved regulatory element of the zebrafish col2a1a gene. Dev Biol 357(2):518–531

    Article  PubMed  CAS  Google Scholar 

  • Dao DY, Yang X, Flick LM, Chen D, Hilton MJ, O’Keefe RJ (2010) Axin2 regulates chondrocyte maturation and axial skeletal development. J Orthop Res 28(1):89–95

    PubMed  CAS  Google Scholar 

  • Dequeant ML, Glynn E, Gaudenz K, Wahl M, Chen J, Mushegian A, Pourquie O (2006) A complex oscillating network of signaling genes underlies the mouse segmentation clock. Science 314(5805):1595–1598

    Article  PubMed  CAS  Google Scholar 

  • Diez del Corral R, Olivera-Martinez I, Goriely A, Gale E, Maden M, Storey K (2003) Opposing FGF and retinoid pathways control ventral neural pattern, neuronal differentiation, and segmentation during body axis extension. Neuron 40(1):65–79

    Article  PubMed  CAS  Google Scholar 

  • DiPaola CP, Farmer JC, Manova K, Niswander LA (2005) Molecular signaling in intervertebral disk development. J Orthop Res 23(5):1112–1119. doi:10.1016/j.orthres.2005.03.008

    Article  PubMed  CAS  Google Scholar 

  • Dobrovolskaia-Zavadskaia N (1927) Sur la mortification spotanee de la chez la souris nouvau-nee et sur l’existence d’un caractere (facteur) herededitaire, non-viable. CR Soc Biol 97:114–116

    Google Scholar 

  • Dockter JL (2000) Sclerotome induction and differentiation. Curr Top Dev Biol 48:77–127

    Article  PubMed  CAS  Google Scholar 

  • Dockter J, Ordahl CP (2000) Dorsoventral axis determination in the somite: a re-examination. Development 127(10):2201–2206

    PubMed  CAS  Google Scholar 

  • Duband JL, Dufour S, Hatta K, Takeichi M, Edelman GM, Thiery JP (1987) Adhesion molecules during somitogenesis in the avian embryo. J Cell Biol 104(5):1361–1374

    Article  PubMed  CAS  Google Scholar 

  • Dubrulle J, Pourquie O (2004) fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo. Nature 427(6973):419–422

    Article  PubMed  CAS  Google Scholar 

  • Dubrulle J, McGrew MJ, Pourquie O (2001) FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell 106(2):219–232

    Article  PubMed  CAS  Google Scholar 

  • Erwin WM (2010) The enigma that is the nucleus pulposus cell: the search goes on. Arthritis Res Ther 12(3):118

    Article  PubMed  Google Scholar 

  • Evrard YA, Lun Y, Aulehla A, Gan L, Johnson RL (1998) Lunatic fringe is an essential mediator of somite segmentation and patterning. Nature 394(6691):377–381

    Article  PubMed  CAS  Google Scholar 

  • Ewan KB, Everett AW (1992) Evidence for resegmentation in the formation of the vertebral column using the novel approach of retroviral-mediated gene transfer. Exp Cell Res 198(2):315–320

    Article  PubMed  CAS  Google Scholar 

  • Fan C-M, Tessier-Lavigne M (1994) Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog. Cell 79(7):1175–1186

    Article  PubMed  CAS  Google Scholar 

  • Ferrer-Vaquer A, Viotti M, Hadjantonakis A-K (2010) Transitions between epithelial and mesenchymal states and the morphogenesis of the early mouse embryo. Cell Adh Migr 4(3):447–457

    Article  PubMed  Google Scholar 

  • Forsberg H, Crozet F, Brown NA (1998) Waves of mouse Lunatic fringe expression, in four-hour cycles at two-hour intervals, precede somite boundary formation. Curr Biol 8(18):1027–1030

    Article  PubMed  CAS  Google Scholar 

  • Gadjanski I, Spiller K, Vunjak-Novakovic G (2012) Time-dependent processes in stem cell-based tissue engineering of articular cartilage. Stem Cell Rev 8(3):863–881

    Article  PubMed  CAS  Google Scholar 

  • Gilson A, Dreger M, Urban JP (2010) Differential expression level of cytokeratin 8 in cells of the bovine nucleus pulposus complicates the search for specific intervertebral disc cell markers. Arthritis Res Ther 12(1):R24

    Article  PubMed  CAS  Google Scholar 

  • Glazier JA, Zhang Y, Swat M, Zaitlen B, Schnell S (2008) Coordinated action of N-CAM, N-cadherin, EphA4, and ephrinB2 translates genetic prepatterns into structure during somitogenesis in chick. Curr Top Dev Biol 81:205–247

    Article  PubMed  Google Scholar 

  • Goldstein RS, Kalcheim C (1992) Determination of epithelial half-somites in skeletal morphogenesis. Development 116(2):441–445

    PubMed  CAS  Google Scholar 

  • Gotz W, Osmers R, Herken R (1995) Localisation of extracellular matrix components in the embryonic human notochord and axial mesenchyme. J Anat 186(Pt 1):111–121

    PubMed  Google Scholar 

  • Haga Y, Dominique VJ, Du SJ (2009) Analyzing notochord segmentation and intervertebral disc formation using the twhh:gfp transgenic zebrafish model. Transgenic Res 18(5):669–683

    Article  PubMed  CAS  Google Scholar 

  • Hayes AJ, Ralphs JR (2011) The response of foetal annulus fibrosus cells to growth factors: modulation of matrix synthesis by TGF-beta1 and IGF-1. Histochem Cell Biol 136(2):163–175

    Article  PubMed  CAS  Google Scholar 

  • Hayes AJ, Benjamin M, Ralphs JR (1999) Role of actin stress fibres in the development of the intervertebral disc: cytoskeletal control of extracellular matrix assembly. Dev Dyn 215(3):179–189

    Article  PubMed  CAS  Google Scholar 

  • Hayes AJ, Isaacs MD, Hughes C, Caterson B, Ralphs JR (2011) Collagen fibrillogenesis in the development of the annulus fibrosus of the intervertebral disc. Eur Cell Mater 22:226–241

    PubMed  CAS  Google Scholar 

  • Huang R, Zhi Q, Wilting J, Christ B (1994) The fate of somitocoele cells in avian embryos. Anat Embryol (Berl) 190(3):243–250

    Article  CAS  Google Scholar 

  • Huang R, Zhi Q, Brand-Saberi B, Christ B (2000) New experimental evidence for somite resegmentation. Anat Embryol (Berl) 202(3):195–200

    Article  CAS  Google Scholar 

  • Iimura T, Denans N, Pourquié O (2009) Chapter 7, Establishment of Hox vertebral identities in the embryonic spine precursors. In: Olivier P (ed) Current topics in developmental biology, vol 88. Academic, New York, pp 201–234

    Google Scholar 

  • Ingham PW, McMahon AP (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15(23):3059–3087

    Article  PubMed  CAS  Google Scholar 

  • Inohaya K, Takano Y, Kudo A (2007) The teleost intervertebral region acts as a growth center of the centrum: in vivo visualization of osteoblasts and their progenitors in transgenic fish. Dev Dyn 236(11):3031–3046

    Article  PubMed  CAS  Google Scholar 

  • Jin H, Shen J, Wang B, Wang M, Shu B, Chen D (2011) TGF-beta signaling plays an essential role in the growth and maintenance of intervertebral disc tissue. FEBS Lett 585(8):1209–1215

    Article  PubMed  CAS  Google Scholar 

  • Johnson RL, Laufer E, Riddle RD, Tabin C (1994) Ectopic expression of Sonic hedgehog alters dorsal-ventral patterning of somites. Cell 79(7):1165–1173

    Article  PubMed  Google Scholar 

  • Johnson J, Rhee J, Parsons SM, Brown D, Olson EN, Rawls A (2001) The anterior/posterior polarity of somites is disrupted in paraxis-deficient mice. Dev Biol 229(1):176–187, S0012-1606(00)99969-X [pii]

    Article  PubMed  CAS  Google Scholar 

  • Johnston SH, Rauskolb C, Wilson R, Prabhakaran B, Irvine KD, Vogt TF (1997) A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway. Development 124(11):2245–2254

    PubMed  CAS  Google Scholar 

  • Kaplan KM, Spivak JM, Bendo JA (2005) Embryology of the spine and associated congenital abnormalities. Spine J 5(5):564–576

    Article  PubMed  Google Scholar 

  • Karasugi T, Semba K, Hirose Y, Kelempisioti A, Nakajima M, Miyake A, Furuichi T, Kawaguchi Y, Mikami Y, Chiba K, Kamata M, Ozaki K, Takahashi A, Makela P, Karppinen J, Kimura T, Kubo T, Toyama Y, Yamamura K, Mannikko M, Mizuta H, Ikegawa S (2009) Association of the tag SNPs in the human SKT gene (KIAA1217) with lumbar disc herniation. J Bone Miner Res 24(9):1537–1543

    Article  PubMed  CAS  Google Scholar 

  • Kawakami Y, Raya A, Raya RM, Rodriguez-Esteban C, Belmonte JC (2005) Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo. Nature 435(7039):165–171

    Article  PubMed  CAS  Google Scholar 

  • Keller R (2000) The origin and morphogenesis of amphibian somites. Curr Top Dev Biol 47(47):183–244

    PubMed  CAS  Google Scholar 

  • Kessel M, Gruss P (1991) Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid. Cell 67(1):89–104

    Article  PubMed  CAS  Google Scholar 

  • Kim DW, Lassar AB (2003) Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. Mol Cell Biol 23(23):8704–8717

    Article  PubMed  CAS  Google Scholar 

  • Kim KW, Lim TH, Kim JG, Jeong ST, Masuda K, An HS (2003) The origin of chondrocytes in the nucleus pulposus and histologic findings associated with the transition of a notochordal nucleus pulposus to a fibrocartilaginous nucleus pulposus in intact rabbit intervertebral discs. Spine (Phila Pa 1976) 28(10):982–990

    Google Scholar 

  • Kim JH, Deasy BM, Seo HY, Studer RK, Vo NV, Georgescu HI, Sowa GA, Kang JD (2009) Differentiation of intervertebral notochordal cells through live automated cell imaging system in vitro. Spine (Phila Pa 1976) 34(23):2486–2493

    Article  Google Scholar 

  • Kispert A, Herrmann BG, Leptin M, Reuter R (1994) Homologs of the mouse Brachyury gene are involved in the specification of posterior terminal structures in Drosophila, Tribolium, and Locusta. Genes Dev 8(18):2137–2150

    Article  PubMed  CAS  Google Scholar 

  • Klippel M, Feil A (1975) The classic: a case of absence of cervical vertebrae with the thoracic cage rising to the base of the cranium (cervical thoracic cage). Clin Orthop Relat Res 109:3–8

    Article  PubMed  Google Scholar 

  • Kmita M, Duboule D (2003) Organizing axes in time and space; 25 years of colinear tinkering. Science 301(5631):331–333

    Article  PubMed  CAS  Google Scholar 

  • Kondo N, Yuasa T, Shimono K, Tung W, Okabe T, Yasuhara R, Pacifici M, Zhang Y, Iwamoto M, Enomoto-Iwamoto M (2011) Intervertebral disc development is regulated by Wnt/beta-catenin signaling. Spine (Phila Pa 1976) 36(8):E513–E518

    Article  Google Scholar 

  • Koob TJ, Long JH (2000) The vertebrate body axis: evolution and mechanical function. Am Zool 40(1):1–18

    Article  Google Scholar 

  • Lee CR, Sakai D, Nakai T, Toyama K, Mochida J, Alini M, Grad S (2007) A phenotypic comparison of intervertebral disc and articular cartilage cells in the rat. Eur Spine J 16(12):2174–2185

    Article  PubMed  Google Scholar 

  • Lefebvre V (2002) Toward understanding the functions of the two highly related Sox5 and Sox6 genes. J Bone Miner Metab 20(3):121–130

    Article  PubMed  CAS  Google Scholar 

  • Lenas P, Moos M, Luyten FP (2009a) Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part I: from three-dimensional cell growth to biomimetics of in vivo development. Tissue Eng Part B Rev 15(4):381–394

    Article  PubMed  Google Scholar 

  • Lenas P, Moos M, Luyten FP (2009b) Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part II: from genes to networks: tissue engineering from the viewpoint of systems biology and network science. Tissue Eng Part B Rev 15(4):395–422

    Article  PubMed  CAS  Google Scholar 

  • Lenas P, Luyten FP, Doblare M, Nicodemou-Lena E, Lanzara AE (2011) Modularity in developmental biology and artificial organs: a missing concept in tissue engineering. Artif Organs 35(6):656–662

    Article  PubMed  Google Scholar 

  • Lettice LA, Purdie LA, Carlson GJ, Kilanowski F, Dorin J, Hill RE (1999) The mouse bagpipe gene controls development of axial skeleton, skull, and spleen. Proc Natl Acad Sci U S A 96(17):9695–9700

    Article  PubMed  CAS  Google Scholar 

  • Li L, Krantz ID, Deng Y, Genin A, Banta AB, Collins CC, Qi M, Trask BJ, Kuo WL, Cochran J, Costa T, Pierpont ME, Rand EB, Piccoli DA, Hood L, Spinner NB (1997) Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet 16(3):243–251

    Article  PubMed  CAS  Google Scholar 

  • Li TF, Darowish M, Zuscik MJ, Chen D, Schwarz EM, Rosier RN, Drissi H, O’Keefe RJ (2006) Smad3-deficient chondrocytes have enhanced BMP signaling and accelerated differentiation. J Bone Miner Res 21(1):4–16

    Article  PubMed  CAS  Google Scholar 

  • Mansouri A, Pla P, Larue L, Gruss P (2001) Pax3 acts cell autonomously in the neural tube and somites by controlling cell surface properties. Development 128(11):1995–2005

    PubMed  CAS  Google Scholar 

  • Marcelle C, Ahlgren S, Bronner-Fraser M (1999) In vivo regulation of somite differentiation and proliferation by sonic hedgehog. Dev Biol 214(2):277–287

    Article  PubMed  CAS  Google Scholar 

  • McCann MR, Tamplin OJ, Rossant J, Seguin CA (2012) Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development. Dis Model Mech 5

    Google Scholar 

  • McGaughran JM, Oates A, Donnai D, Read AP, Tassabehji M (2003) Mutations in PAX1 may be associated with Klippel-Feil syndrome. Eur J Hum Genet 11(6):468–474

    Article  PubMed  CAS  Google Scholar 

  • Minogue BM, Richardson SM, Zeef LA, Freemont AJ, Hoyland JA (2010) Characterization of the human nucleus pulposus cell phenotype and evaluation of novel marker gene expression to define adult stem cell differentiation. Arthritis Rheum 62(12):3695–3705

    Article  PubMed  Google Scholar 

  • Mittapalli VR, Huang R, Patel K, Christ B, Scaal M (2005) Arthrotome: a specific joint forming compartment in the avian somite. Dev Dyn 234(1):48–53

    Article  PubMed  Google Scholar 

  • Monsoro-Burq AH (2005) Sclerotome development and morphogenesis: when experimental embryology meets genetics. Int J Dev Biol 49(2–3):301–308

    Article  PubMed  CAS  Google Scholar 

  • Monsoro-Burq AH, Bontoux M, Teillet MA, Le Douarin NM (1994) Heterogeneity in the development of the vertebra. Proc Natl Acad Sci U S A 91(22):10435–10439

    Article  PubMed  CAS  Google Scholar 

  • Moore KL, Oersaud TVN (2003) Before we are born, 6th edn. Saunders, Philadelphia

    Google Scholar 

  • Morimoto M, Takahashi Y, Endo M, Saga Y (2005) The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity. Nature 435(7040):354–359. doi:10.1038/nature03591

    Article  PubMed  CAS  Google Scholar 

  • Muller TS, Ebensperger C, Neubuser A, Koseki H, Balling R, Christ B, Wilting J (1996) Expression of avian Pax1 and Pax9 is intrinsically regulated in the pharyngeal endoderm, but depends on environmental influences in the paraxial mesoderm. Dev Biol 178(2):403–417

    Article  PubMed  CAS  Google Scholar 

  • Murtaugh LC, Chyung JH, Lassar AB (1999) Sonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling. Genes Dev 13(2):225–237

    Article  PubMed  CAS  Google Scholar 

  • Naiche LA, Holder N, Lewandoski M (2011) FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis. Proc Natl Acad Sci 108(10):4018–4023

    Article  PubMed  CAS  Google Scholar 

  • Oda T, Elkahloun AG, Pike BL, Okajima K, Krantz ID, Genin A, Piccoli DA, Meltzer PS, Spinner NB, Collins FS, Chandrasekharappa SC (1997) Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet 16(3):235–242

    Article  PubMed  CAS  Google Scholar 

  • Oldershaw RA, Baxter MA, Lowe ET, Bates N, Grady LM, Soncin F, Brison DR, Hardingham TE, Kimber SJ (2010) Directed differentiation of human embryonic stem cells toward chondrocytes. Nat Biotechnol 28(11):1187–1194

    Article  PubMed  CAS  Google Scholar 

  • Paavola LG, Wilson DB, Center EM (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

    PubMed  CAS  Google Scholar 

  • Palmeirim I, Henrique D, Ish-Horowicz D, Pourquié O (1997) Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis. Cell 91(5):639–648

    Article  PubMed  CAS  Google Scholar 

  • Patil AS, Sable RB, Kothari RM (2011) An update on transforming growth factor-beta (TGF-beta): sources, types, functions and clinical applicability for cartilage/bone healing. J Cell Physiol 226(12):3094–3103

    Article  PubMed  CAS  Google Scholar 

  • Peacock A (1951) Observations on the prenatal development of the intervertebral disc in man. J Anat 85(3):260–274

    PubMed  CAS  Google Scholar 

  • Pelton RW, Dickinson ME, Moses HL, Hogan BL (1990) In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2. Development 110(2):609–620

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Pourquie O (2011) Vertebrate segmentation: from cyclic gene networks to scoliosis. Cell 145(5):650–663

    Article  PubMed  CAS  Google Scholar 

  • Radice GL, Rayburn H, Matsunami H, Knudsen KA, Takeichi M, Hynes RO (1997) Developmental defects in mouse embryos lacking N-cadherin. Dev Biol 181(1):64–78

    Article  PubMed  CAS  Google Scholar 

  • Reaume AG, Conlon RA, Zirngibl R, Yamaguchi TP, Rossant J (1992) Expression analysis of a Notch homologue in the mouse embryo. Dev Biol 154(2):377–387

    Article  PubMed  CAS  Google Scholar 

  • Rider CC, Mulloy B (2010) Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists. Biochem J 429(1):1–12

    Article  PubMed  CAS  Google Scholar 

  • Risbud MV, Schaer TP, Shapiro IM (2010) Toward an understanding of the role of notochordal cells in the adult intervertebral disc: from discord to accord. Dev Dyn 239(8):2141–2148

    Article  PubMed  CAS  Google Scholar 

  • Rodrigo I, Hill RE, Balling R, Munsterberg A, Imai K (2003) Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Development 130(3):473–482

    Article  PubMed  CAS  Google Scholar 

  • Rufai A, Benjamin M, Ralphs JR (1995) The development of fibrocartilage in the rat intervertebral disc. Anat Embryol (Berl) 192(1):53–62

    Article  CAS  Google Scholar 

  • Saga Y (2007) Segmental border is defined by the key transcription factor Mesp2, by means of the suppression of notch activity. Dev Dyn 236(6):1450–1455

    Article  PubMed  CAS  Google Scholar 

  • Saga Y, Hata N, Koseki H, Taketo MM (1997) Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation. Genes Dev 11(14):1827–1839

    Article  PubMed  CAS  Google Scholar 

  • Sakai Y, Meno C, Fujii H, Nishino J, Shiratori H, Saijoh Y, Rossant J, Hamada H (2001) The retinoic acid-inactivating enzyme CYP26 is essential for establishing an uneven distribution of retinoic acid along the anterio-posterior axis within the mouse embryo. Genes Dev 15(2):213–225

    Article  PubMed  CAS  Google Scholar 

  • Sakai D, Nakai T, Mochida J, Alini M, Grad S (2009) Differential phenotype of intervertebral disc cells: microarray and immunohistochemical analysis of canine nucleus pulposus and anulus fibrosus. Spine (Phila Pa 1976) 34(14):1448–1456

    Article  Google Scholar 

  • Sasaki N, Kiso M, Kitagawa M, Saga Y (2011) The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis. Development 138(1):55–64

    Article  PubMed  CAS  Google Scholar 

  • Sawada A, Shinya M, Jiang YJ, Kawakami A, Kuroiwa A, Takeda H (2001) Fgf/MAPK signalling is a crucial positional cue in somite boundary formation. Development 128(23):4873–4880

    PubMed  CAS  Google Scholar 

  • Scaal M, Wiegreffe C (2006) Somite compartments in anamniotes. Anat Embryol (Berl) 211(Suppl 1):9–19

    Google Scholar 

  • Schweitzer R, Chyung JH, Murtaugh LC, Brent AE, Rosen V, Olson EN, Lassar A, Tabin CJ (2001) Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments. Development 128(19):3855–3866

    PubMed  CAS  Google Scholar 

  • Scotti C, Tonnarelli B, Papadimitropoulos A, Scherberich A, Schaeren S, Schauerte A, Lopez-Rios J, Zeller R, Barbero A, Martin I (2010) Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering. Proc Natl Acad Sci U S A 107(16):7251–7256

    Article  PubMed  CAS  Google Scholar 

  • Semba K, Araki K, Li Z, Matsumoto K, Suzuki M, Nakagata N, Takagi K, Takeya M, Yoshinobu K, Araki M, Imai K, Abe K, Yamamura K (2006) A novel murine gene, Sickle tail, linked to the Danforth’s short tail locus, is required for normal development of the intervertebral disc. Genetics 172(1):445–456

    Article  PubMed  CAS  Google Scholar 

  • Senthinathan B, Sousa C, Tannahill D, Keynes R (2012) The generation of vertebral segmental patterning in the chick embryo. J Anat 220(6):591–602

    Article  PubMed  Google Scholar 

  • Serra R, Chang C (2003) TGF-beta signaling in human skeletal and patterning disorders. Birth Defects Res C Embryo Today 69(4):333–351

    Article  PubMed  CAS  Google Scholar 

  • Serra R, Johnson M, Filvaroff EH, LaBorde J, Sheehan DM, Derynck R, Moses HL (1997) Expression of a truncated, kinase-defective TGF-b type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J Cell Biol 139:541–552

    Article  PubMed  CAS  Google Scholar 

  • Settle SH Jr, Rountree RB, Sinha A, Thacker A, Higgins K, Kingsley DM (2003) Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Dev Biol 254(1):116–130

    Article  PubMed  CAS  Google Scholar 

  • Shapiro IM, Risbud MV (2010) Transcriptional profiling of the nucleus pulposus: say yes to notochord. Arthritis Res Ther 12(3):117

    Article  PubMed  CAS  Google Scholar 

  • Shen B, Bhargav D, Wei A, Williams LA, Tao H, Ma DD, Diwan AD (2009) BMP-13 emerges as a potential inhibitor of bone formation. Int J Biol Sci 5(2):192–200

    Article  PubMed  Google Scholar 

  • Shi S, Ciurli C, Cartman A, Pidoux I, Poole AR, Zhang Y (2003) Experimental immunity to the G1 domain of the proteoglycan versican induces spondylitis and sacroiliitis, of a kind seen in human spondylarthropathies. Arthritis Rheum 48(10):2903–2915

    Article  PubMed  CAS  Google Scholar 

  • Shifley ET, Cole SE (2007) The vertebrate segmentation clock and its role in skeletal birth defects. Birth Defects Res C Embryo Today 81(2):121–133

    Article  PubMed  CAS  Google Scholar 

  • Sirbu IO, Duester G (2006) Retinoic-acid signalling in node ectoderm and posterior neural plate directs left-right patterning of somitic mesoderm. Nat Cell Biol 8(3):271–277

    Article  PubMed  CAS  Google Scholar 

  • Smits P, 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(6):1135–1148

    Article  PubMed  CAS  Google Scholar 

  • Smits P, Li P, Mandel J, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B, Lefebvre V (2001) The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev Cell 1(2):277–290

    Article  PubMed  CAS  Google Scholar 

  • Sohn P, Cox M, Chen D, Serra R (2010) Molecular profiling of the developing mouse axial skeleton: a role for Tgfbr2 in the development of the intervertebral disc. BMC Dev Biol 10(1):29

    Article  PubMed  CAS  Google Scholar 

  • Sporle R, Schughart K (1998) Paradox segmentation along inter- and intrasomitic borderlines is followed by dysmorphology of the axial skeleton in the open brain (opb) mouse mutant. Dev Genet 22(4):359–373

    Article  PubMed  CAS  Google Scholar 

  • Stafford DA, Brunet LJ, Khokha MK, Economides AN, Harland RM (2011) Cooperative activity of noggin and gremlin 1 in axial skeleton development. Development 138(5):1005–1014

    Article  PubMed  CAS  Google Scholar 

  • Stemple DL (2005) Structure and function of the notochord: an essential organ for chordate development. Development 132(11):2503–2512

    Article  PubMed  CAS  Google Scholar 

  • Stott D, Kispert A, Herrmann BG (1993) Rescue of the tail defect of Brachyury mice. Genes Dev 7(2):197–203

    Article  PubMed  CAS  Google Scholar 

  • Swiatek PJ, Lindsell CE, del Amo FF, Weinmaster G, Gridley T (1994) Notch1 is essential for postimplantation development in mice. Genes Dev 8(6):707–719

    Article  PubMed  CAS  Google Scholar 

  • Swiderski RE, Solursh M (1992) Localization of type II collagen, long form alpha 1(IX) collagen, and short form alpha 1(IX) collagen transcripts in the developing chick notochord and axial skeleton. Dev Dyn 194(2):118–127. doi:10.1002/aja.1001940205

    Article  PubMed  CAS  Google Scholar 

  • Tassabehji M, Fang ZM, Hilton EN, McGaughran J, Zhao Z, de Bock CE, Howard E, Malass M, Donnai D, Diwan A, Manson FDC, Murrell D, Clarke RA (2008) Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. Hum Mutat 29(8):1017–1027

    Article  PubMed  CAS  Google Scholar 

  • Theiler K (1988) Vertebral malformations. Adv Anat Embryol Cell Biol 112:1–99

    Article  PubMed  CAS  Google Scholar 

  • Tracy MR, Dormans JP, Kusumi K (2004) Klippel-Feil syndrome: clinical features and current understanding of etiology. Clin Orthop Relat Res 424:183–190

    Article  PubMed  Google Scholar 

  • Tribioli C, Lufkin T (1999) The murine Bapx1 homeobox gene plays a critical role in embryonic development of the axial skeleton and spleen. Development 126(24):5699–5711

    PubMed  CAS  Google Scholar 

  • Turnpenny PD (2008) Defective somitogenesis and abnormal vertebral segmentation in man. Adv Exp Med Biol 638:164–189

    Article  PubMed  CAS  Google Scholar 

  • Vermot J, Pourquie O (2005) Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos. Nature 435(7039):215–220

    Article  PubMed  CAS  Google Scholar 

  • Vermot J, Gallego Llamas J, Fraulob V, Niederreither K, Chambon P, Dolle P (2005) Retinoic acid controls the bilateral symmetry of somite formation in the mouse embryo. Science 308(5721):563–566

    Article  PubMed  CAS  Google Scholar 

  • Vilhais-Neto GC, Maruhashi M, Smith KT, Vasseur-Cognet M, Peterson AS, Workman JL, Pourquie O (2010) Rere controls retinoic acid signalling and somite bilateral symmetry. Nature 463(7283):953–957

    Article  PubMed  CAS  Google Scholar 

  • Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM (2006) Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol 209(2):157–165

    Article  PubMed  CAS  Google Scholar 

  • Wahl MB, Deng C, Lewandoski M, Pourquié O (2007) FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis. Development 134(22):4033–4041

    Article  PubMed  CAS  Google Scholar 

  • Wamsley R (1953) Development and growth of the intervertebral disc. Edinb Med J 60:341–363

    Google Scholar 

  • Wei A, Williams LA, Bhargav D, Shen B, Kishen T, Duffy N, Diwan AD (2009) BMP13 prevents the effects of annular injury in an ovine model. Int J Biol Sci 5(5):388–396

    Article  PubMed  CAS  Google Scholar 

  • Wellik DM (2007) Hox patterning of the vertebrate axial skeleton. Dev Dyn 236(9):2454–2463

    Article  PubMed  CAS  Google Scholar 

  • Wellik DM (2009) Chapter 9, Hox genes and vertebrate axial pattern. In: Olivier P (ed) Current topics in developmental biology, vol 88. Academic, New York, pp 257–278

    Google Scholar 

  • Wiggan O, Fadel MP, Hamel PA (2002) Pax3 induces cell aggregation and regulates phenotypic mesenchymal-epithelial interconversion. J Cell Sci 115(Pt 3):517–529

    PubMed  CAS  Google Scholar 

  • Willard DP, Nicholson JT (1934) The Klippel-Feil syndrome. Ann Surg 99(4):561–567

    Article  PubMed  CAS  Google Scholar 

  • Williams LW (1910) The somites of the chick. Am J Anat 11:55–100

    Article  Google Scholar 

  • Wrana JL, Attisano L, Wieser R, Ventura F, Massague J (1994) Mechanism of activation of the TGF-beta receptor. Nature 370(6488):341–347

    Article  PubMed  CAS  Google Scholar 

  • Yang XR, Ng D, Alcorta DA, Liebsch NJ, Sheridan E, Li S, Goldstein AM, Parry DM, Kelley MJ (2009) T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet 41(11):1176–1178

    Article  PubMed  CAS  Google Scholar 

  • Yoon BS, Ovchinnikov DA, Yoshii I, Mishina Y, Behringer RR, Lyons KM (2005) Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo. Proc Natl Acad Sci U S A 102(14):5062–5067

    Article  PubMed  CAS  Google Scholar 

  • Ytteborg E, Torgerson J, Baeverfjord G, Takle H (2012) Chapter 14, The Atlantic salmon (Salmo salar) vertebra and cellular pathways to vertebral deformities. In: Carvalho ED, David GS, Silva RJ (eds) Health and environment in aquaculture. Intech, Rijeka

    Google Scholar 

  • Zakany J, Kmita M, Alarcon P, de la Pompa JL, Duboule D (2001) Localized and transient transcription of Hox genes suggests a link between patterning and the segmentation clock. Cell 106(2):207–217

    Article  PubMed  CAS  Google Scholar 

  • Zakin L, Metzinger CA, Chang EY, Coffinier C, De Robertis EM (2008) Development of the vertebral morphogenetic field in the mouse: interactions between Crossveinless-2 and Twisted Gastrulation. Dev Biol 323(1):6–18

    Article  PubMed  CAS  Google Scholar 

  • Zakin L, Chang EY, Plouhinec JL, De Robertis EM (2010) Crossveinless-2 is required for the relocalization of Chordin protein within the vertebral field in mouse embryos. Dev Biol 347(1):204–215

    Article  PubMed  CAS  Google Scholar 

  • Zeng L, Kempf H, Murtaugh LC, Sato ME, Lassar AB (2002) Shh establishes an Nkx3.2/Sox9 autoregulatory loop that is maintained by BMP signals to induce somitic chondrogenesis. Genes Dev 16(15):1990–2005. doi:10.1101/gad.1008002

    Article  PubMed  CAS  Google Scholar 

  • Zhang N, Gridley T (1998) Defects in somite formation in lunatic fringe-deficient mice. Nature 394(6691):374–377

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Spine research in Dr. Serra’s laboratory is supported by a grant from the National Institutes of Health, R01AR053860. MC is supported by NIDCR Training Grant (DART) T32-DE0176707. The authors would like to thank Zak Kosan for the help with the figures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rosa Serra .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Wien

About this chapter

Cite this chapter

Cox, M.K., Serra, R. (2014). Development of the Intervertebral Disc. In: Shapiro, I., Risbud, M. (eds) The Intervertebral Disc. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1535-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-1535-0_3

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-1534-3

  • Online ISBN: 978-3-7091-1535-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics