ECTOPIC LOCALIZATION OF NEURAL CREST CELLS: ETIOLOGICAL FACTOR OF SCOLIOSIS

Objective. To identify cell phenotypes in vertebral body growth plates from patients with idiopathic scoliosis.

Material and Methods. Cells were isolated from vertebral body growth plates both on convex and concave sides of the deformity in patients operated on for scoliosis. Cells were cultured and identified by methods of common morphology, neuromorphology, electron microscopy, immunohistochemistry, and PCR analysis.

Results. Cultured cells obtained from the convex side of the deformity were identified as chondroblasts. Cells isolated from growth plates on the concave side of the deformity were described as neuro- and glioblasts. Cells formed synapses, contained neurofilaments, and expressed neural and glial proteins, respectively.

Conclusion. Ectopic localization of neural crest-derived cells in vertebral body growth plates is the etiological factor for scoliotic disease. 

1. Зайдман А.М. Идиопатический сколиоз. Морфология, биохимия, генетика. Новосибирск, 1993.

2. Зайдман А.М., Михайловский М.В., Садовой М.А. Нейрофиброматоз и сколиоз. Новосибирск, 2011.

3. Зайдман А.М., Строкова Е.Л., Новиков В.В., Васюра А.С., Михайловский М.В., Садовой М.А. Экспрессия генов в хондроцитах пластинки роста у пациентов с идиопатическим сколиозом // Хирургия позвоночника. 2014. № 4. С. 88-98.

4. Карлсон Б.М. Основы эмбриологии по Пэттену. М., 1983.

5. Кнорре А.Г. Эмбриональный гистогенез. Л., 1971.

6. Токин Б.П. Общая эмбриология. М., 1977.

7. Bronner-Fraser M, Garcia-Castro M. Manipulations of neural crest cells or their migratory pathways. Methods Cell Biol. 2008;87:75-96. DOI: 10.1016/S0091-679X (08)00204-5.

8. Bundy J, Rogers R, Hoffman S, Conway SJ. Segmental expression of aggrecan in the non-segmented perinotochordal sheath underlies normal segmentation of the vertebral column. Mech Dev. 1998;79:213-7.

9. Dayer R, Haumont T, Belaieff W, Lascombes P. Idiopathic scoliosis: etiological concepts and hypotheses. J Child Orthop. 2013;7:11-16. DOI: 10.1007/s11832-012-0458-3.

10. Erickson CA, Perris R. The role of cell-cell and cell-matrix interactions in the morphogenesis of the neural crest. Dev Biol. 1993;159:60-74. DOI: 10.1006/dbio.1993.1221.

11. Gorman KF, Julien C, Moreau A. The genetic epidemiology of idiopathic scoliosis. Eur Spine J. 2012;21:1905-1919. DOI: 10.1007/s00586-012-2389-6.

12. Guo X, Chau WW, Hui-Chan CW, Cheung CS, Tsang WW, Cheng JC. Balance control in adolescents with idiopathic scoliosis and disturbed somatosensory function. Spine. 2006;31:E437-E440. DOI: 10.1097/01.brs.0000222048.47010.bf.

13. Henderson DJ, Ybot-Gonzalez P, Copp AJ. Over-expression of the chondroitin sulphate proteoglycan versican is associated with defective neural crest migration in the Pax3 mutant mouse (splotch). Mech Dev. 1997;69:39-51. DOI: 10.1016/S0925-4773(97)00151-2.

14. Krull CE. Inhibitory interactions in the patterning of trunk neural crest migration. Ann NY Acad Sci. 1998;857:13-22.

15. Krull CE, Collazo A, Fraser SE, Bronner-Fraser M. Segmental migration of trunk neural crest: time-lapse analysis reveals a role for PNA-binding molecules. Development. 1995;121:3733-3743.

16. Le Douarin NM, Teillet MA. Experimental analysis of the migration and differentiation of neuroblasts of the autonomic nervous system and of neurectodermal mesenchymal derivatives, using a biological cell marking technique. Dev Biol. 1974;41:162-184. DOI: 10.1016/0012-1606(74)90291-7.

17. Logan M, Martin JF, Nagy A, Lobe C, Olson EN, Tabin CJ. Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis. 2002;33:77-80. DOI: 10.1002/gene.10092.

18. Machida M, Dubousset J, Yamada T, Kimura J. Serum melatonin levels in adolescent idiopathic scoliosis prediction and prevention for curve progression - a prospective study. J Pineal Res. 2009;46:344-348. DOI: 10.1111/j.1600-079X.2009.00669.x.

19. McGonnell IM, Graham A. Trunk neural crest has skeletogenic potential. Curr Biol. 2002;12:767-771. DOI: 10.1016/S0960-9822(02)00818-7.

20. Miller NH. Idiopathic scoliosis: cracking the genetic code and what does it mean? J Pediatr Orthop. 2011;31(1 Suppl):S49-S52. DOI: 10.1097/BPO.0b013e318202bfe2.

21. Ogilvie JW. Update on prognostic genetic testing in adolescent idiopathic scoliosis (AIS). J Pediatr Orthop. 2011;31(1 Suppl):S46-S48. DOI: 10.1097/BPO. 0b013e3181fd87eb.

22. Peris R, Perissinotto D. Role of the extracellular matrix during neural crest cell migration. Mech Dev. 2000;95:3-21. DOI: 10.1016/S0925-4773(00)00365-8.

23. Pettway Z, Domowicz M, Schwartz NB, Bronner-Fraser M. Age-dependent inhibition of neural crest migration by the notochord correlates with alteration in the S103L chondroitin sulfate proteoglycan. Exp Cell Res. 1996;255:195-206. DOI: 10.1006/excr.1996.0170.

24. Porter RW. The pathogenesis of idiopathic scoliosis: uncoupled neuro-osseous growth? Eur Spine J. 2001;10:473-481.

25. Roffers-Agarwal J, Gammill LS. Neuropilin receptors guide distinct phases of sensory and motor neuronal segmentation. Development. 2009;136:1879-1888. DOI: 10.1242/dev.032920.

26. Salehi LB, Mangino M, De Serio S, De Cicco D, Capon F, Semprini S, Pizzuti A, Novelli G, Dallapiccola B. Assignment of a locus for autosomal dominant idiopathic scoliosis (IS) to human chromosome 17p11. Hum Genet. 2002;111:401-404. DOI: 10.1007/s00439-002-0785-4.

27. Stokes IA, Burwell RG, Dangerfield PH. Biomechanical spinal growth modulation and progressive adolescent scoliosis - a test of the “vicious cycle” pathogenetic hypothesis: summery of an electronic focus group debate of the IBSE. Scoliosis. 2006;1:16. DOI: 10.1186/1748-7161-1-16.

28. Veldhuizen AG, Wever DJ, Webb PJ. The aetiology of idiopathic scoliosis: biomechanical and neuromuscular factors. Eur Spine J 2000;9:178-184. DOI: 10.1007/s005860000142.

29. Wise CA, Gao X, Shoemaker S, Gordon N, Herring JA. Understanding genetic factors in idiopathic scoliosis, a complex dislase of childhood. Curr Genomics. 2008; 9:51-59. DOI: 10.2174/138920208783884874.