Anterior Hox genes interact with components of the neural crest specification network to induce neural crest fates

Stem Cells. 2011 May;29(5):858-70. doi: 10.1002/stem.630.


Hox genes play a central role in neural crest (NC) patterning particularly in the cranial region of the body. Despite evidence that simultaneous loss of Hoxa1 and Hoxb1 function resulted in NC specification defects, the role of Hox genes in NC specification has remained unclear due to extended genetic redundancy among Hox genes. To circumvent this problem, we expressed anterior Hox genes in the trunk neural tube of the developing chick embryo. This demonstrated that anterior Hox genes play a central role in NC cell specification by rapidly inducing the key transcription factors Snail2 and Msx1/2 and a neural progenitor to NC cell fate switch characterized by cell adhesion changes and an epithelial-to-mesenchymal transition (EMT). Cells delaminated from dorsal and medial neural tube levels and generated ectopic neurons, glia progenitors, and melanocytes. The mobilization of the NC genetic cascade was dependent upon bone morphogenetic protein signaling and optimal levels of Notch signaling. Therefore, anterior Hox patterning genes participate in NC specification and EMT by interacting with NC-inducing signaling pathways and regulating the expression of key genes involved in these processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation / physiology
  • Chick Embryo
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • In Situ Hybridization
  • MSX1 Transcription Factor / genetics
  • MSX1 Transcription Factor / metabolism
  • Mice
  • Neural Crest / cytology*
  • Neural Crest / metabolism*
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Bone Morphogenetic Proteins
  • HOXB1 homeodomain protein
  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • MSX1 protein, human
  • MSX2 protein
  • SNAI1 protein, human
  • Snai1 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors