Current perspectives of the signaling pathways directing neural crest induction

Cell Mol Life Sci. 2012 Nov;69(22):3715-37. doi: 10.1007/s00018-012-0991-8. Epub 2012 May 1.


The neural crest is a migratory population of embryonic cells with a tremendous potential to differentiate and contribute to nearly every organ system in the adult body. Over the past two decades, an incredible amount of research has given us a reasonable understanding of how these cells are generated. Neural crest induction involves the combinatorial input of multiple signaling pathways and transcription factors, and is thought to occur in two phases from gastrulation to neurulation. In the first phase, FGF and Wnt signaling induce NC progenitors at the border of the neural plate, activating the expression of members of the Msx, Pax, and Zic families, among others. In the second phase, BMP, Wnt, and Notch signaling maintain these progenitors and bring about the expression of definitive NC markers including Snail2, FoxD3, and Sox9/10. In recent years, additional signaling molecules and modulators of these pathways have been uncovered, creating an increasingly complex regulatory network. In this work, we provide a comprehensive review of the major signaling pathways that participate in neural crest induction, with a focus on recent developments and current perspectives. We provide a simplified model of early neural crest development and stress similarities and differences between four major model organisms: Xenopus, chick, zebrafish, and mouse.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Chick Embryo
  • Embryonic Induction*
  • Epithelial-Mesenchymal Transition
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental*
  • MAP Kinase Signaling System*
  • Mice
  • Morphogenesis
  • Neural Crest / embryology*
  • Neural Plate / embryology*
  • Receptors, Notch / metabolism
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*
  • Xenopus laevis / embryology
  • Zebrafish / embryology


  • Bone Morphogenetic Proteins
  • Receptors, Notch
  • Wnt Proteins
  • Fibroblast Growth Factors