Journal of Biosciences

, 33:781 | Cite as

The neural crest and neural crest cells: discovery and significance for theories of embryonic organization



The neural crest has long fascinated developmental biologists, and, increasingly over the past decades, evolutionary and evolutionary developmental biologists. The neural crest is the name given to the fold of ectoderm at the junction between neural and epidermal ectoderm in neurula-stage vertebrate embryos. In this sense, the neural crest is a morphological term akin to head fold or limb bud. This region of the dorsal neural tube consists of neural crest cells, a special population(s) of cell, that give rise to an astonishing number of cell types and to an equally astonishing number of tissues and organs. Neural crest cell contributions may be direct — providing cells — or indirect — providing a necessary, often inductive, environment in which other cells develop. The enormous range of cell types produced provides an important source of evidence of the neural crest as a germ layer, bringing the number of germ layers to four — ectoderm, endoderm, mesoderm, and neural crest. In this paper I provide a brief overview of the major phases of investigation into the neural crest and the major players involved, discuss how the origin of the neural crest relates to the origin of the nervous system in vertebrate embryos, discuss the impact on the germ-layer theory of the discovery of the neural crest and of secondary neurulation, and present evidence of the neural crest as the fourth germ layer. A companion paper (Hall, Evol. Biol. 2008) deals with the evolutionary origins of the neural crest and neural crest cells.


Cell types discovery germ layers natural crest 


  1. Beck C W and Slack J M W 1998 Analysis of the developing Xenopus tail bud reveals separate phases of gene expression during determination and outgrowth; Mech. Dev. 72 41–52PubMedCrossRefGoogle Scholar
  2. Beck C W and Slack J M W 1999 A developmental pathway controlling outgrowth of the Xenopus tail bud; Development 126 1611–1620PubMedGoogle Scholar
  3. de Beer G R 1947 The differentiation of neural crest cells into visceral cartilages and odontoblasts in Amblystoma, and a reexamination of the germ-layer theory; Proc. R. Soc. London B134 377–398CrossRefGoogle Scholar
  4. de Beer G R 1971 Homology: An unsolved problem, Oxford Biology Reader No. 11 (London: Oxford University Press)Google Scholar
  5. Billon N, Iannarelli P, Monteiro M C, Glavieux-Pardanaud C, et al 2007 The generation of adipocytes by the neural crest; Development 134 2283–2292PubMedCrossRefGoogle Scholar
  6. Bolande R P 1974 The neurocristopathies: A unifying concept of disease arising in neural crest maldevelopment Human Pathol. 5 409–429CrossRefGoogle Scholar
  7. Bolande R P 1981 Neurofibromatosis:-the quintessential neurocristopathy: Pathogenetic concepts and relationships; Adv. Neurol. 29 67–75PubMedGoogle Scholar
  8. Carroll S B, Grenier J K and Weatherbee S D 2005 From DNA to Diversity. Molecular genetics and the Evolution of Animal Design. Second Edition. Blackwell Publishing, Malden, MA.Google Scholar
  9. Carstens M H 2004 Neural tube programming and craniofacial cleft formation. I. The neuromeric organization of the head and neck; Eur. J. Pediatr. Neurol. 8 181–210CrossRefGoogle Scholar
  10. Ebendal T 1995 Cell movement in neurogenesis — An interview with Professor Jacobson, Carl Olaf; Int. J. Dev. Biol. 39 705–711Google Scholar
  11. Eberhart J K, He X, Swartz M E, Yan Y-L, et al 2008 MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis Nat. Genet. 40 290–298PubMedCrossRefGoogle Scholar
  12. Eberhart J K, Swartz M E, Crump G and Kimmel C B 2006 Early hedgehog signaling from neural to oral epithelium organizes anterior craniofacial development; Development 133 1069–1077PubMedCrossRefGoogle Scholar
  13. Gans C and Northcutt R G 1983 Neural crest and the origin of vertebrates: a new head; Science 220 268–274PubMedCrossRefGoogle Scholar
  14. Griffith C M, Wiley M J and Sanders E J 1992 The vertebrate tail bud: Three germ layers from one tissue; Anat. Embryol. 185 101–113PubMedCrossRefGoogle Scholar
  15. Grüneberg H 1956 A ventral ectodermal ridge of the tail in mouse embryos Nature (London) 177 787–788CrossRefGoogle Scholar
  16. Gurdon J B 1992 The generation of diversity and pattern in animal development; Cell 68 185–199PubMedCrossRefGoogle Scholar
  17. Halder G, Callaerts P and Gehring W J 1995. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila; Science 267 1788–1792PubMedCrossRefGoogle Scholar
  18. Hall B K (ed.) 1994 Homology: The hierarchical basis of comparative biology (Boca Raton: Academic Press)Google Scholar
  19. Hall B K 1995 Homology and embryonic development; Evol. Biol. 28 1–37Google Scholar
  20. Hall B K 1998 Germ layers and the germ-layer theory revisited: Primary and secondary germ layers, neural crest as a fourth germ layer, homology, demise of the germ-layer theory; Evol. Biol. 30 121–186Google Scholar
  21. Hall B K 1999a The neural crest in development and evolution (New York: Springer)Google Scholar
  22. Hall B K 1999b Evolutionary developmental biology 2nd edition (Dordrecht, Netherlands: Kluwer Academic Publishers)Google Scholar
  23. Hall B K 2000a A role for epithelial-mesenchymal interactions in tail growth/morphogenesis and chondrogenesis in embryonic mice; Cell Tissues Organs 166 6–14CrossRefGoogle Scholar
  24. Hall B K 2000b The evolution of the neural crest in vertebrates; in Regulatory processes in development: The legacy of sven Hörstadius Wenner-Gren International Series Volume 76 (eds) C-O Jacobson, L Olsson and T Laurent (London: The Portland Press) pp 101–113Google Scholar
  25. Hall B K 2000c Epithelial-mesenchymal interactions; in Methods in molecular biology, Vol. 125: Developmental biology protocols, Vol. 3 (eds) R S Tuan and C W Lo) (Totowa, NJ: Humana Press Inc.) pp 235–243Google Scholar
  26. Hall B K 2000d The neural crest as a fourth germ layer and vertebrates as quadroblastic not triploblastic; Evol. Dev. 2 1–3CrossRefGoogle Scholar
  27. Hall B K 2003a Unlocking the Black Box between Genotype and Phenotype: Cell Condensations as Morphogenetic (modular) Units; Biol. Philos. 18 219–247CrossRefGoogle Scholar
  28. Hall B K 2005b Bone and cartilage: Developmental and evolutionary skeletal biology (London: Elsevier Academic Press)Google Scholar
  29. Hall B K 2007 Homology and homoplasy; in Handbook of the philosophy of science. Philosophy of biology (eds) M Matthen and C Stephens (Elsevier B V) pp 429–453Google Scholar
  30. Hall B K 2008a The neural crest and neural crest cells in vertebrate development and evolution (New York: Springer) (in press)Google Scholar
  31. Hall B K 2008b Evolutionary origins of the neural crest and neural crest cells; Evol. Biol. (in press)Google Scholar
  32. Hall B K and Hallgrímsson B (ed.) 2008 Strickberger’s evolution. The integration of genes, organisms, and populations 4th edition (Sudbury, MA: Jones and Bartlett, Publishers)Google Scholar
  33. Handrigan G R 2003 Concordia discors: duality in the origin of the vertebrate tail; J. Anat. 202 255–267PubMedGoogle Scholar
  34. Heimberg A M, Sempere L F, Moy V N, Donoghue P C J and Peterson K J 2008 MicroRNAs and the advent of vertebrate morphological complexity; Proc. Natl. Acad. Sci. USA 105 2946–2950PubMedCrossRefGoogle Scholar
  35. Holland P W H and Graham A 1995 Evolution of regional identity in the vertebrate nervous system; Persp. Dev. Neurobiol. 3 17–27Google Scholar
  36. Holmdahl D E 1928 Die Enstehung und weitere Entwicklung der Neuralleiste (Ganglienleiste) bei Vogeln und Saugetieren; Z. Mikrosk-Anat. Forsch. 14 99–298Google Scholar
  37. Hörstadius S 1950 The neural vrest: Its properties and derivatives in the light of experimental research (Oxford: Oxford University Press)Google Scholar
  38. Hörstadius S and Sellman S 1941 Experimental studies on the determination of the chondrocranium in Amblystoma mexicanum; Ark. Zool. 33A 1–8Google Scholar
  39. Hörstadius S and Sellman S 1946 Experimentelle untersuchungen über die Determination des Knorpeligen Kopfskelettes bei Urodelen; Nova Acta R. Soc. Scient. Upsal. Ser. 4, 13 1–170Google Scholar
  40. Jacobson C-O 2000 Sven Hörstadius, the man and his work; in Regulatory processes in development (eds) L Olsson and C-O Jacobson (London: Portland Press) pp 1–10Google Scholar
  41. Janvier P 2007 Homologies and evolutionary transitions in early vertebrate history; in Major transitions in vertebrate evolution (eds) J S Anderson and H-D Sues (Bloomington and Indianapolis: Indiana University Press) pp 57–121Google Scholar
  42. Johnson D R 1986 The genetics of the skeleton. Animal models of skeletal development (Oxford: The Clarendon Press)Google Scholar
  43. Johnston M C 1966 A radioautographic study of the migration and fate of cranial neural crest cells in the chick embryo; Anat. Rec. 156 143–156PubMedCrossRefGoogle Scholar
  44. Kang P and Svoboda K K H 2005 Epithelial-mesenchymal transformation during craniofacial development; J. Dental Res. 84 678–690CrossRefGoogle Scholar
  45. Kerr J G 1919. Text-book of embryology, Volume II. Vertebrata with the exception of mammalia (London: Macmillan)Google Scholar
  46. Landacre F L 1921 The fate of the neural crest in the head of the Urodeles J. Comp. Neurol. 33 1–43CrossRefGoogle Scholar
  47. Lankester E R 1873 On the primitive cell-layers of the embryo as the basis of genealogical classification of animals, and on the origin of vascular and lymph systems; Ann. Mag. Nat. Hist. Series 4 11 321–338Google Scholar
  48. Lankester E R 1877 Notes on the embryology and classification of the animal kingdom: Comprising a revision of speculations relative to the origin and significance of the germ layers; Quart. J. Microsc. Sci. 17 399–454Google Scholar
  49. Le Douarin N M 1974 Cell recognition based on natural morphological nuclear markers; Med. Biol. 52 281–319PubMedGoogle Scholar
  50. Le Douarin N M 1982 The neural crest (Cambridge: Cambridge University Press)Google Scholar
  51. Le Douarin N M 1986 Cell line segregation during peripheral nervous system ontogeny; Science 231 1515–1522PubMedCrossRefGoogle Scholar
  52. Le Douarin N M, Dupin E, Baroffio A and Dulac C 1992 New insights into the development of neural crest derivatives; Int. Rev. Cytol. 138 269–314PubMedCrossRefGoogle Scholar
  53. Le Douarin N M, Grapin-Botton A and Catala M 1996 Patterning of the neural primordium in the avian embryo; Sem. Cell Dev. Biol. 1 157–167Google Scholar
  54. Le Douarin N M and Kalcheim C 1999 The neural crest 2nd edition (Cambridge: Cambridge University Press)Google Scholar
  55. Maderson P F A (ed.) 1987 Developmental and evolutionary aspects of the neural crest (New York: John Wiley)Google Scholar
  56. Martindale M Q, Pang K and Finnerty J R 2004 Investigating the origins of triploblasty: ‘mesodermal’ gene expression in a diploblastic animal, the sea anemone Nematostella vectensis (phylum, Cnidaria; class, Anthozoa); Development 131 2463–2474PubMedCrossRefGoogle Scholar
  57. Miller C T, Beleza S, Pollen. A, Schluter D, et al 2007 cisregulatory changes in Kit Ligand expression and parallel evolution of pigmentation in sticklebacks and humans; Cell 131 1179–1189PubMedCrossRefGoogle Scholar
  58. Mohanty-Hejmadi P, Dutta S K and Mahapatra P 1992 Limbs generated at site of tail amputation in marbled balloon frog after vitamin A treatment; Nature (London) 355 352–353CrossRefGoogle Scholar
  59. Morales A V, Barbas J A and Nieto M A 2005 How to become neural crest: From segregation to delamination; Sem. Cell Dev. Biol. 16 655–662CrossRefGoogle Scholar
  60. Müller F and O’Rahilly R 2004 The primitive streak, the caudal eminence and related structures in staged human embryos; Cells Tissues Organs 177 2–20PubMedCrossRefGoogle Scholar
  61. Newgreen D F (ed.) 1995 Epithelial-Mesenchymal transitions, Part I; Acta Anat. 154 1–97Google Scholar
  62. Olsson L 2000 The scientific publications of Sven Hörstadius — a bibliography; in Regulatory processes in development (ed.) L Olsson and C-O Jacobson (London: Portland Press) pp 11–18Google Scholar
  63. Opitz J M and Clark E B 2000 Heart development: an introduction; Am. J. Med. Gen. 97 238–247CrossRefGoogle Scholar
  64. Oppenheimer J M 1940 The non-specificity of the germ layers; Q. Rev. Biol. 15 1–27CrossRefGoogle Scholar
  65. O’Rahilly R and Müller F 2006 The embryonic human brain: An Atlas of developmental stages 3rd edition (New York: Wiley-Liss)Google Scholar
  66. O’Rahilly R and Müller F 2007 The development of the neural crest in the human; J. Anat. 211 335–351PubMedCrossRefGoogle Scholar
  67. Peterson K J and Davidson E H 2000 Regulatory evolution and the origin of the bilaterians; Proc. Natl. Acad. Sci. USA 97 4430–4433PubMedCrossRefGoogle Scholar
  68. Peterson P E, Blankenship T H, Wilson D B and Hendrickx A G 1996 Analysis of hindbrain neural crest migration in the long-tailed monkey (Macaca fascicularis); Anat. Embryol. 194 235–246PubMedCrossRefGoogle Scholar
  69. Platt J B 1893 Ectodermic origin of the cartilages of the head; Anat. Anz. 8 506–509Google Scholar
  70. Platt J B 1894 Ontogenetic differentiation of the ectoderm in Necturus. Second preliminary note; Arch. Mikrosk. Anat. EntwMech. 43 911–966CrossRefGoogle Scholar
  71. Platt J B 1897 The development of the cartilaginous skull and of the branchial and hypoglossal musculature in Necturus; Morphol. Jb. 25 377–464Google Scholar
  72. Putnam N H, Srivastava M, Hellsten U, Dirks B, et al 2007 Sea anemone genome reveals ancestral eumetazoan gene repertoires and genomic organization; Science 317 86–95PubMedCrossRefGoogle Scholar
  73. Raven C P 1931 Zur Entwicklung der Ganglienleiste. I. Die Kinematik der Ganglienleisten Entwicklung bei den Urodelen; Wilhelm Roux Arch. EntwMech Org. 125 210–293CrossRefGoogle Scholar
  74. Raven C P 1936 Zur Entwicklung der Ganglienleiste. V. über die Differenzierung des Rumpfganglienleistenmaterials; Wilhelm Roux Arch. EntwMech Org. 134 122–145CrossRefGoogle Scholar
  75. Remak R 1850–1855 Untersuchungen über die Entwickelung der Wirbelthiere (Berlin: G Reimer)Google Scholar
  76. Sasai Y and de Robertis E M 1997 Ectodermal patterning in vertebrate embryos; Dev. Biol. 182 5–20PubMedCrossRefGoogle Scholar
  77. Savagner P 2001 Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition; BioEssays 23 912–923PubMedCrossRefGoogle Scholar
  78. Schaeffer B 1977 The dermal skeleton in fishes; in Problems in vertebrate evolution (eds) S M Andrews, R S Miles and A D Walker Linn. Soc. Symp. 4 25–52Google Scholar
  79. Schoenwolf G C, Chandler N B and Smith J L 1985 Analysis of the origins and early fates of neural crest cells in caudal regions of avian embryos; Dev. Biol. 110 467–479PubMedCrossRefGoogle Scholar
  80. Schoenwolf G C and Nichols D H 1984 Histological and ultrastructural studies on the origin of caudal neural crest cells in mouse embryos; J. Comp. Neurol. 222 496–505PubMedCrossRefGoogle Scholar
  81. Shimeld S M, and Holland P W H 2000 Vertebrate innovations; Proc. Natl. Acad. Sci. USA 97 4449–4452PubMedCrossRefGoogle Scholar
  82. Stone J R, and Hall B K 2004 Latent homologues for the neural crest as an evolutionary novelty. Evol. Dev. 6 123–129PubMedCrossRefGoogle Scholar
  83. Stone L S 1926 Further experiments on the extirpation and transplantation of mesectoderm in Amblystoma punctatum; J. Exp. Zool. 44 95–131CrossRefGoogle Scholar
  84. Stone L S 1929 Experiments showing the role of migrating neural crest (mesectoderm) in the formation of head skeleton and loose connective tissue in Rana palustris; Wilhelm Roux Arch. EntwMech Org. 118 40–77CrossRefGoogle Scholar
  85. Takashima Y, Era T, Nakao K, Kondo S, et al 2007 Neuroepithelial cells supply an initial transient wave of MSC differentiation; Cell 129 1377–1388PubMedCrossRefGoogle Scholar
  86. Vickaryous M K and Hall B K 2006 Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest Biol. Rev. Camb. Philos. Soc. 81 425–455PubMedCrossRefGoogle Scholar
  87. Weston J A 1963 A radioautographic analysis of the migration and localization of trunk neural crest cells in the chick; Dev. Biol. 6 279–310PubMedCrossRefGoogle Scholar
  88. Weston J A 1970 The migration and differentiation of neural crest cells; Adv. Morphog. 8 41–114PubMedGoogle Scholar
  89. Weston J A, Yoshida H, Robinson V B, Nishikawa S et al 2004 Neural crest and the origin of ectomesenchyme: neural fold heterogeneity suggests an alternative hypothesis; Dec. Dyn. 229 118–130CrossRefGoogle Scholar
  90. Wilson D B and Wyatt D P 1988 Closure of the posterior neuropore in the vL mutant mouse. Anat Embryol. 178 559–563PubMedCrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2008

Authors and Affiliations

  1. 1.Department of BiologyDalhousie UniversityHalifaxCanada

Personalised recommendations