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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Spine

  • Aldh1a2 haploinsufficiency prevents the appearance of spina bifida and rescues the development of posterior structures (sacral/caudal vertebrae, hindgut, urogenital tract), while partly preventing cervical vertebral transformations and hindbrain pattern alterations in Cyp26a1(-/-) mice [1].
  • Since Sim2 mRNA is expressed in facial, skull, palate and vertebra primordia in human and rodent embryos, features that are associated with phenotypes of Down's syndrome (DS), its trisomic state is suspected to contribute to the symptoms of DS [2].
  • MATERIALS AND METHODS: A total of 103 patients with initial diagnosis of lung cancer was prospectively examined with planar bone scintigraphy (BS), SPECT of the vertebral column and PET using F-18 sodium fluoride (F-18 PET) [3].
  • Mice lacking both Gdf5 and Gdf6 show additional defects, including severe reduction or loss of some skeletal elements in the limb, additional fusions between skeletal structures, scoliosis, and altered cartilage in the intervertebral joints of the spinal column [4].
  • We report a 12-yr-old boy without a history of steroid use, in whom severe osteoporosis and multiple collapsed vertebrae were the presenting manifestations of Crohn's disease [5].

High impact information on Spine

  • Further expression analysis of Pitx3 in the mouse supports a unique role in early ocular development, with later expression extending to the midbrain, tongue, incisors, sternum, vertebrae and limbs [6].
  • Hoxb-4 (Hox-2.6) mutant mice show homeotic transformation of a cervical vertebra and defects in the closure of the sternal rudiments [7].
  • The murine paired box gene Pax-1 has been associated with the mouse developmental mutant undulated (un), which exhibits malformations in the vertebral column [8].
  • Exposure of murine embryos to teratogenic doses of retinoic acid (RA) induced homeotic transformations of vertebrae [9].
  • We found evidence in the records of a total of 58 fractures of the ribs or vertebrae in 14 of the patients who had received long-term steroid treatment (11 per cent) and no evidence of fractures in the patients who had not received long-term treatment [10].

Chemical compound and disease context of Spine

  • Osteopenia and dynamic tetracycline-based estimates of increased bone turnover in ovariectomized animals were more pronounced in the proximal tibia relative to the lumbar vertebra [11].
  • Channel catfish fingerlings fed purified diets devoid of vitamin C showed reduced growth rate, deformed spinal columns, external and internal hemorrhages, erosion of fins, dark skin color and reduced bone collagen content after 8 to 12 weeks, whereas fish fed a diet containing 30 mg/kg of vitamin C had none of these anomalies after 22 weeks [12].
  • Cervical MR imaging disclosed an extra-medullary intradural crooked shadow at the level between C2 and C3 vertebrae, which was proven by selective angiogram of the ascending cervical artery to be a dural arteriovenous malformation located in the right C3 root sleeve [13].
  • We report on a family with autosomal dominant coronal synostosis, segmentation and fusion anomalies of the vertebra and ribs, and Sprengel shoulder due to the Pro250Arg mutation [14].
  • MATERIALS AND METHODS: Twenty-five patients with spinal compression fractures underwent routine spinal MRI with an additional (1)H MRS study protocol to assess the percent fat fraction of the compressed vertebrae as well as the adjacent bony environment [15].

Biological context of Spine


Anatomical context of Spine

  • Pax 1, a murine paired box-containing gene, is expressed in ventral sclerotome cells and later in intervertebral disks along the entire vertebral column [16].
  • Early defects are observed in the establishment or maintenance of midline structures, such as the notochord and the floorplate, and later defects include absence of distal limb structures, cyclopia, absence of ventral cell types within the neural tube, and absence of the spinal column and most of the ribs [21].
  • We show here that expression of Hoxa10 in the presomitic mesoderm is sufficient to confer a Hox group 10 patterning program to the somite, producing vertebrae without ribs, an effect not achieved when Hoxa10 is expressed in the somites [22].
  • The osteogenic sarcomas were often multiple and appeared predominantly in the facial bones, less frequently in the ribs and vertebral column, and only rarely in the appendicular skeleton [23].
  • We conclude that Pax-1 is necessary for normal vertebral column formation along the entire axis, although the severity of the phenotype is strongest in the lumbar region and the tail [24].

Associations of Spine with chemical compounds

  • After in vivo double tetracycline labeling, bone histomorphometry by standard methods was performed on one femur and one tail vertebra [25].
  • The antisera were labeled with fluorescein and applied to sections of muscles from various vertebrae species [26].
  • PHY increased, by over 3-fold, the spontaneous activity of reticulospinal cardiovascular neurons in the C1 area which excite preganglionic sympathetic neurons in the intermediolateral spinal column [27].
  • Loading of rat vertebrae and ulnae produces increases in NO2- release, and in ulnae NO synthase inhibitors diminish these responses [28].
  • The density of peripheral-type benzodiazepine receptors and adenosine A1 receptors was dramatically increased (250-300%) in the lateral and ventral spinal columns, reflecting the proliferation of glial cells [29].

Gene context of Spine

  • Thus, Lmx1a is required for development of the roof plate and, in turn, for specification of dorsal cell fates in the CNS and developing vertebrae [30].
  • Disruption of Fgfr3 results in prolonged growth of long bones and vertebrae [31].
  • No MESP2 mutations were found in a further 7 patients with related radiological phenotypes in whom abnormal segmentation affected all vertebrae, nor in a further 12 patients with diverse phenotypes [32].
  • Btg2-null mice are viable and fertile but exhibit posterior homeotic transformations of the axial vertebrae in a dose-dependent manner [33].
  • Analysis of bone ossification in newborn Pex7(-/-) mice revealed a defect in ossification of distal bone elements of the limbs as well as parts of the skull and vertebrae [34].

Analytical, diagnostic and therapeutic context of Spine


  1. Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development. Niederreither, K., Abu-Abed, S., Schuhbaur, B., Petkovich, M., Chambon, P., Dollé, P. Nat. Genet. (2002) [Pubmed]
  2. Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16: an animal model of Down's syndrome. Ema, M., Ikegami, S., Hosoya, T., Mimura, J., Ohtani, H., Nakao, K., Inokuchi, K., Katsuki, M., Fujii-Kuriyama, Y. Hum. Mol. Genet. (1999) [Pubmed]
  3. F-18 NaF PET for detection of bone metastases in lung cancer: accuracy, cost-effectiveness, and impact on patient management. Hetzel, M., Arslandemir, C., König, H.H., Buck, A.K., Nüssle, K., Glatting, G., Gabelmann, A., Hetzel, J., Hombach, V., Schirrmeister, H. J. Bone Miner. Res. (2003) [Pubmed]
  4. Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Settle, S.H., Rountree, R.B., Sinha, A., Thacker, A., Higgins, K., Kingsley, D.M. Dev. Biol. (2003) [Pubmed]
  5. Osteoporosis: an unusual presentation of childhood Crohn's disease. Thearle, M., Horlick, M., Bilezikian, J.P., Levy, J., Gertner, J.M., Levine, L.S., Harbison, M., Berdon, W., Oberfield, S.E. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  6. A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Semina, E.V., Ferrell, R.E., Mintz-Hittner, H.A., Bitoun, P., Alward, W.L., Reiter, R.S., Funkhauser, C., Daack-Hirsch, S., Murray, J.C. Nat. Genet. (1998) [Pubmed]
  7. Hoxb-4 (Hox-2.6) mutant mice show homeotic transformation of a cervical vertebra and defects in the closure of the sternal rudiments. Ramírez-Solis, R., Zheng, H., Whiting, J., Krumlauf, R., Bradley, A. Cell (1993) [Pubmed]
  8. The molecular basis of the undulated/Pax-1 mutation. Chalepakis, G., Fritsch, R., Fickenscher, H., Deutsch, U., Goulding, M., Gruss, P. Cell (1991) [Pubmed]
  9. Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid. Kessel, M., Gruss, P. Cell (1991) [Pubmed]
  10. Steroid-induced fractures and bone loss in patients with asthma. Adinoff, A.D., Hollister, J.R. N. Engl. J. Med. (1983) [Pubmed]
  11. Histologic evidence for osteopenia and increased bone turnover in ovariectomized rats. Wronski, T.J., Walsh, C.C., Ignaszewski, L.A. Bone (1986) [Pubmed]
  12. Pathology of the vitamin C deficiency syndrome in channel catfish (Ictalurus punctatus). Lim, C., Lovell, R.T. J. Nutr. (1978) [Pubmed]
  13. Cervical dural arteriovenous malformation presenting with right-sided occipitalgia: before and after successful treatment by embolization. Chiba, S., Nishioka, H., Saitoh, M., Imai, T., Tanabe, S., Matsumoto, H. Headache. (1994) [Pubmed]
  14. Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel shoulder with and without Pro250Arg mutation in the FGFR3 gene. Lowry, R.B., Jabs, E.W., Graham, G.E., Gerritsen, J., Fleming, J. Am. J. Med. Genet. (2001) [Pubmed]
  15. Vertebrae adjacent to spinal bone lesion are inconsistent reference markers: A magnetic resonance spectroscopic viewpoint. Rumpel, H., Chan, L.L., Chan, L.P., Png, M.A., Tan, R.K., Lim, W.E. Journal of magnetic resonance imaging : JMRI. (2006) [Pubmed]
  16. undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax 1. Balling, R., Deutsch, U., Gruss, P. Cell (1988) [Pubmed]
  17. Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation. Rancourt, D.E., Tsuzuki, T., Capecchi, M.R. Genes Dev. (1995) [Pubmed]
  18. Tumor necrosis factor enhances parathyroid hormone-related protein-induced hypercalcemia and bone resorption without inhibiting bone formation in vivo. Uy, H.L., Mundy, G.R., Boyce, B.F., Story, B.M., Dunstan, C.R., Yin, J.J., Roodman, G.D., Guise, T.A. Cancer Res. (1997) [Pubmed]
  19. Mice transgenic for the human carcinoembryonic antigen gene maintain its spatiotemporal expression pattern. Eades-Perner, A.M., van der Putten, H., Hirth, A., Thompson, J., Neumaier, M., von Kleist, S., Zimmermann, W. Cancer Res. (1994) [Pubmed]
  20. Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton. Favier, B., Rijli, F.M., Fromental-Ramain, C., Fraulob, V., Chambon, P., Dollé, P. Development (1996) [Pubmed]
  21. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Chiang, C., Litingtung, Y., Lee, E., Young, K.E., Corden, J.L., Westphal, H., Beachy, P.A. Nature (1996) [Pubmed]
  22. Hox genes specify vertebral types in the presomitic mesoderm. Carapuço, M., Nóvoa, A., Bobola, N., Mallo, M. Genes Dev. (2005) [Pubmed]
  23. Transgenic mouse model for neurocristopathy: Schwannomas and facial bone tumors. Jensen, N.A., Rodriguez, M.L., Garvey, J.S., Miller, C.A., Hood, L. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  24. The role of Pax-1 in axial skeleton development. Wallin, J., Wilting, J., Koseki, H., Fritsch, R., Christ, B., Balling, R. Development (1994) [Pubmed]
  25. Calcitriol but no other metabolite of vitamin D is essential for normal bone growth and development in the rat. Parfitt, A.M., Mathews, C.H., Brommage, R., Jarnagin, K., DeLuca, H.F. J. Clin. Invest. (1984) [Pubmed]
  26. "Slow" myosins in vertebrae skeletal muscle. An immunofluorescence study. Bormioli, S.P., Sartore, S., Vitadello, M., Schiaffino, S. J. Cell Biol. (1980) [Pubmed]
  27. Cholinergic regulation of arterial pressure by the C1 area of the rostral ventrolateral medulla. Giuliano, R., Ruggiero, D.A., Morrison, S., Ernsberger, P., Reis, D.J. J. Neurosci. (1989) [Pubmed]
  28. Mechanical strain-induced NO production by bone cells: a possible role in adaptive bone (re)modeling? Pitsillides, A.A., Rawlinson, S.C., Suswillo, R.F., Bourrin, S., Zaman, G., Lanyon, L.E. FASEB J. (1995) [Pubmed]
  29. Receptor alterations associated with spinal motoneuron degeneration in bovine Akabane disease. Gundlach, A.L., Grabara, C.S., Johnston, G.A., Harper, P.A. Ann. Neurol. (1990) [Pubmed]
  30. The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS. Millonig, J.H., Millen, K.J., Hatten, M.E. Nature (2000) [Pubmed]
  31. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Ohbayashi, N., Shibayama, M., Kurotaki, Y., Imanishi, M., Fujimori, T., Itoh, N., Takada, S. Genes Dev. (2002) [Pubmed]
  32. Mutated MESP2 causes spondylocostal dysostosis in humans. Whittock, N.V., Sparrow, D.B., Wouters, M.A., Sillence, D., Ellard, S., Dunwoodie, S.L., Turnpenny, P.D. Am. J. Hum. Genet. (2004) [Pubmed]
  33. B-cell translocation gene 2 (Btg2) regulates vertebral patterning by modulating bone morphogenetic protein/smad signaling. Park, S., Lee, Y.J., Lee, H.J., Seki, T., Hong, K.H., Park, J., Beppu, H., Lim, I.K., Yoon, J.W., Li, E., Kim, S.J., Oh, S.P. Mol. Cell. Biol. (2004) [Pubmed]
  34. Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata. Brites, P., Motley, A.M., Gressens, P., Mooyer, P.A., Ploegaert, I., Everts, V., Evrard, P., Carmeliet, P., Dewerchin, M., Schoonjans, L., Duran, M., Waterham, H.R., Wanders, R.J., Baes, M. Hum. Mol. Genet. (2003) [Pubmed]
  35. The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse. Oh, S.P., Li, E. Genes Dev. (1997) [Pubmed]
  36. Modulation of osteogenic cell ultrastructure by RS-23581, an analog of human parathyroid hormone (PTH)-related peptide-(1-34), and bovine PTH-(1-34). Leaffer, D., Sweeney, M., Kellerman, L.A., Avnur, Z., Krstenansky, J.L., Vickery, B.H., Caulfield, J.P. Endocrinology (1995) [Pubmed]
  37. Patient variables and the subarachnoid spread of hyperbaric bupivacaine in the term parturient. Norris, M.C. Anesthesiology (1990) [Pubmed]
  38. Bone turnover in early rheumatoid arthritis. 2. Longitudinal bone density studies. Sambrook, P.N., Ansell, B.M., Foster, S., Gumpel, J.M., Hesp, R., Reeve, J. Ann. Rheum. Dis. (1985) [Pubmed]
  39. Direct stereological estimation of three-dimensional connectivity in rat vertebrae: effect of estrogen, etidronate and risedronate following ovariectomy. Boyce, R.W., Wronski, T.J., Ebert, D.C., Stevens, M.L., Paddock, C.L., Youngs, T.A., Gundersen, H.J. Bone (1995) [Pubmed]
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