Anatomy and Embryology

, Volume 209, Issue 5, pp 349–355 | Cite as

Wnts and the neural crest



The neural crest is a multipotent tissue that originates between the neural epithelium and non-neural ectoderm, which can develop into numerous cell types, including neurons, glia, pigment cells, smooth muscle, cartilage and bone. Work in a variety of animal models has shown that a number of signalling factors are necessary for the induction, delamination and differentiation of neural crest cells. However one family of proteins, the Wnts, shows an overriding influence on this tissue. Here we review recent studies that pinpoint specific roles that Wnts play in the development of the neural crest.


Wnts Neural crest Induction Delamination Differentiation 


  1. Aoki Y, Saint-Germain N, Gyda M, Magner-Fink E, Lee YH, Credidio C, Saint-Jeannet JP (2003) Sox10 regulates the development of neural crest-derived melanocytes in Xenopus. Dev Biol 259:19–33PubMedGoogle Scholar
  2. Baker CV, Bronner-Fraser M (1997) The origins of the neural crest. Part I: embryonic induction. Mech Dev 69:3–11PubMedGoogle Scholar
  3. Bastidas F, De Callisto J, Mayor R (2001) Identification of neural crest competence territory: role of Wnt signaling. Dev Dyn 229:109–117CrossRefGoogle Scholar
  4. Bhanot P, Brink M, Samos CH, Hsieh JC, Wang Y, Macke JP, Andrew D, Nathans J, Nusse R (1996) A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382:225–230CrossRefPubMedGoogle Scholar
  5. Bonstein L, Elias S, Frank D (1998) Paraxial-fated mesoderm is required for neural crest induction in Xenopus embryos. Dev Biol 193:156–168CrossRefPubMedGoogle Scholar
  6. Britsch S, Goerich DE, Riethmacher D, Peirano RI, Rossner M, Nave KA, Birchmeier C, Wegner M (2001) The transcription factor Sox10 is a key regulator of peripheral glial development. Gen Dev 15:66–78Google Scholar
  7. Bronner-Fraser M (1986) Analysis of the early stages of trunk neural crest migration in avian embryos using monoclonal antibody HNK-1. Dev Biol 115:44–55CrossRefPubMedGoogle Scholar
  8. Burstyn-Cohen T, Stanleigh J, Sela-Donenfeld D, Kalcheim C (2004) Canonical Wnt activity regulates trunk neural crest delamination linking BMP/Noggin signalling with G1/S transition. Development 131:5327–5339PubMedGoogle Scholar
  9. Carl TF, Dufton C, Hanken J, Klymkowsky MW (1999) Inhibition of neural crest migration in Xenopus using antisense slug RNA. Dev Biol 213:101–115PubMedGoogle Scholar
  10. Chang C, Hemmati-Brivanlou A (1998) Neural crest induction by Xwnt7b in Xenopus. Dev Biol 194:129–134CrossRefPubMedGoogle Scholar
  11. Coles E, Christiansen J, Economou A, Bronner-Fraser M (2004) A vertebrate crossveinless 2 homologue modulates BMP activity and neural crest migration. Development 131:5309–5317PubMedGoogle Scholar
  12. Deardorff MA, Tan C, Saint-Jeannet JP, Klein PS (2001) A role for frizzled 3 in neural crest development. Development 128:3655–3663PubMedGoogle Scholar
  13. Del Barrio MG, Nieto MA (2002) Overexpression of Snail family members highlights their ability to promote chick neural crest formation. Development 129:1583–1593PubMedGoogle Scholar
  14. Dickinson ME, Selleck AJ, McMahon AP, Bronner-Fraser M (1995) Dorsalization of the neural tube by the non-neural ectoderm. Development 121:2099–2106PubMedGoogle Scholar
  15. Dorsky RI, Moon RT, Raible DW (1998) Control of neural crest cell fate by the Wnt signalling pathway. Nature 396:370–373PubMedGoogle Scholar
  16. Dorsky RI, Raible DW, Moon RT (2000) Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway. Gen Dev 14:158–162Google Scholar
  17. Dunn KJ, Williams BO, Li Y, Pavan WJ (2000) Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development. Proc Natl Acad Sci USA 18:10050–10055CrossRefGoogle Scholar
  18. Dutton KA, Pauliny A, Lopes SS, Elworthy S, Carney TJ, Rauch J, Geisler R, Haffter P, Kelsh RN (2001) Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates. Development 128:4113–4125PubMedGoogle Scholar
  19. Garcia-Castro MI, Marcelle C, Bronner-Fraser M (2002) Ectodermal Wnt function as a neural crest inducer. Science 297:848–851PubMedGoogle Scholar
  20. Hamburger V, Hamilton HL (1951) A series of normal stages in the development of the chick embryo. J Morphol 88:49–92CrossRefGoogle Scholar
  21. Hari L, Brault V, Kleber M, Lee HY, Ille F, Leimeroth R, Paratore C, Suter U, Kemler R, Sommer L (2002) Lineage-specific requirements of ß-catenin in neural crest development. J Cell Biol 159:867–880PubMedGoogle Scholar
  22. Hay ED (1995) An overview of epithelio-mesenchymal transformation. Acta Anat (Basel) 154:8–20Google Scholar
  23. He X, Saint-Jeannet JP, Wang Y, Nathans J, Dawid I, Varmus H (1997) A member of the frizzled family mediating axis induction by Wnt-5A. Science 275:1652–1654CrossRefPubMedGoogle Scholar
  24. Honore SM, Aybar MJ, Mayor R (2003) Sox10 is required for the early development of the prospective neural crest in Xenopus embryos. Dev Biol 260:79–96PubMedGoogle Scholar
  25. Huang X, Saint-Jeannet JP (2004) Induction of the neural crest and the opportunities of life on the edge. Dev Biol 275:1–11PubMedGoogle Scholar
  26. Jin EJ, Erickson CA, Takada S, Burrus LW (2001) Wnt and BMP signaling govern lineage segregation of melanocytes in the avian embryo. Dev Biol 233:22–37PubMedGoogle Scholar
  27. Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Science 116:2627–2634PubMedGoogle Scholar
  28. Kelsh RN, Schmid B, Eisen JS (2000) Genetic analysis of melanophore development in zebrafish embryos. Dev Biol 225:277–293PubMedGoogle Scholar
  29. La Bonne C, Bronner Fraser M (2000) Snail-related transcriptional repressors are required in Xenopus for both the induction of the induction of the neural crest and its subsequent migration. Dev Biol 221:195–205PubMedGoogle Scholar
  30. La Bonne C, Bronner-Fraser M (1998) Neural crest induction in Xenopus: evidence for a two-signal model. Development 125:2403–2414PubMedGoogle Scholar
  31. Le Douarin NM (2004) The avian embryo as a model to study the development of the neural crest: a long and still ongoing story. Mech Dev 121:1089–102CrossRefPubMedGoogle Scholar
  32. Lee HY, Kleber M, Hari L, Brault V, Suter U, Taketo MM, Kemler R, Sommer L (2004) Instructive role of Wnt/ß-catenin in sensory fate specification in neural crest stem cells. Science 303:1020–1023PubMedGoogle Scholar
  33. Lewis JL, Bonner J, Modrell M, Ragland JW, Moon RT, Dorsky RI, Raible DW (2003) Reiterated Wnt signalling during zebrafish neural crest development. Development 131:1299–1308CrossRefGoogle Scholar
  34. Liem KF, Tremml G, Roelink H, Jessel TM (1995) Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm. Cell 82:969–79CrossRefPubMedGoogle Scholar
  35. Liu JP, Jessell TM (1998) A role for rhoB in the delamination of neural crest cells from the dorsal neural tube. Development 125:5055–5067PubMedGoogle Scholar
  36. Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X (2002) Control of beta catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108:837–847CrossRefPubMedGoogle Scholar
  37. Major R, Morgan R, Sargent M (1995) Induction of the prospective neural crest of Xenopus. Development 121:767–777PubMedGoogle Scholar
  38. Marchant L, Linker C, Ruiz P, Guerro N, Mayor R (1998) The inductive properties of mesoderm suggest that the neural crest cells are specified by a BMP gradient. Dev Biol 198:319–329PubMedGoogle Scholar
  39. McGonnell IM, Graham A (2002) Trunk neural crest has skeletogenic potential. Curr Biol 12:767–771CrossRefPubMedGoogle Scholar
  40. Monsoro-Burq AH, Fletcher RB, Harland RM (2003) Neural crest induction by paraxial mesoderm in Xenopus embryos requires FGF signals. Development 130:3111–3124CrossRefPubMedGoogle Scholar
  41. Moon RT, Bowerman B, Boutros M, Perrimon N (2002) The promise and perils of Wnt signalling through beta-catenin. Science 296:1644–1646CrossRefPubMedGoogle Scholar
  42. Muroyama Y, Fujihara M, Ikeya M, Kondoh H, Takada S (2002) Wnt signalling plays an essential role in neuronal specification of the dorsal spinal cord. Gen Dev 16:548–553Google Scholar
  43. Nieto MA, Sargent MG, Wilkinson DG, Cooke J (1994) Control of cell behaviour during vertebrate development by slug, a zinc finger gene. Science 264:835–839PubMedGoogle Scholar
  44. Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Prehu MO, Puliti A, Herbarth B, Hermans-Borgmeyer I, Legius E, Matthijs G (1998) Sox10 mutations in patients with Waardenburg-Hirschsprung disease. Nat Genet 18:171–173PubMedGoogle Scholar
  45. Pingault V, Guiochon-Mantel A, Bondurand N, Faure C, Lacroix C, Lyonnet S, Goossens M, Landrieu P (2000) Peripheral neuropathy with hypomyelination, chronic intestinal pseudo-obstruction and deafness: a developmental “neural crest syndrome” related to Sox10 mutation. Ann Neurol 48:671–676CrossRefPubMedGoogle Scholar
  46. Polakis P (2002) Casein kinase 1: a Wnt’er of disconnect. Curr Biol 12:R499-R501CrossRefPubMedGoogle Scholar
  47. Saint-Jeannet JP, He X, Varmus HE, Dawid IB (1997) Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a. Proc Natl Acad Sci USA 94:13713–13718PubMedGoogle Scholar
  48. Savagner P (2001) Leaving the neighbourhood: molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays 23:912–923PubMedGoogle Scholar
  49. Sela-Donenfeld D, Kalcheim C (1999) Regulation of the onset of neural crest migration by coordinated activity of BMP4 and Noggin in the dorsal neural tube. Development 126:4749–4762PubMedGoogle Scholar
  50. Sela-Donenfeld D, Kalcheim C (2000) Inhibition of Noggin expression in the dorsal neural tube by somitogenesis: a mechanism for coordinating the timing of neural crest emigration. Development 127:4845–4854PubMedGoogle Scholar
  51. Selleck MAJ, Bronner-Fraser M (1995) Origins of the avian neural crest: the role of neural plate-epidermal interactions. Development 121:525–538PubMedGoogle Scholar
  52. Selleck MAJ, Bronner-Fraser M (2000) Neural crest cell fate decisions: a diffusible signal mediates induction of neural crest by the ectoderm. Int J Dev Neuroscience 18:621–627Google Scholar
  53. Southard-Smith EM, Kos L, Pavan WJ (1998) Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nat Genet 18:60–64PubMedGoogle Scholar
  54. Tachibana M (2000) MITF: a stream flowing for pigment cells. Pigment Cell Res 13:230–240PubMedGoogle Scholar
  55. Takeda K, Yasumoto K, Takada R, Takada S, Watanabe K, Udono T, Saito H, Takahashi K, Shibahara S (2000) Induction of melanocyte-specific microophthalmia-associated transcription factor by Wnt-3a. J Biol Chem 19:14013–14016CrossRefGoogle Scholar
  56. Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X (2000)LDL-receptro related proteins in Wnt signal transduction. Nature 407:530–535PubMedGoogle Scholar
  57. Vallin J, Thuret R, Giacomello E, Faraldo MM, Thiery JP, Broders F (2001) Cloning and characterization of three Xenopus slug promoter reveal direct regulation by Lef/ß-catenin signalling. J Biol Chem 32:30350–30358CrossRefGoogle Scholar
  58. Villanueva S, Glavic A, Ruiz P, Mayor R (2002) Posteriorization by FGF, Wnt, and retinoic acid is required for neural crest induction. Dev Biol 241:289–301PubMedGoogle Scholar
  59. Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene 341:19–39PubMedGoogle Scholar
  60. Wodarz A, Nusse R (1998) Mechanisms of Wnt signalling in development. Annu Rev Cell Biol 14:59–88Google Scholar
  61. Yasumoto K, Takeda K Saito H, Watanabe K, Takahashi K, Shibahara S (2002) Microophthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signalling. EMBO J 11:2703–2714CrossRefGoogle Scholar
  62. Yoshikawa Y, Fujumori T, McMahon AP, Takada S (1997) Evidence that absence of Wnt-3a signalling promotes neuralization instead of paraxial mesoderm development in the mouse. Dev Biol 183:234–242PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Veterinary Basic SciencesThe Royal Veterinary CollegeLondonUK
  2. 2.Institute of AnatomyLudwigs-Maximillians-University of MunichMunichGermany

Personalised recommendations