Zebrafish Cdx4 regulates neural crest cell specification and migratory behaviors in the posterior body

Dev Biol. 2021 Dec:480:25-38. doi: 10.1016/j.ydbio.2021.08.002. Epub 2021 Aug 11.


The neural crest (NC) is a transient multipotent cell population that migrates extensively to produce a remarkable array of vertebrate cell types. NC cell specification progresses in an anterior to posterior fashion, resulting in distinct, axial-restricted subpopulations. The anterior-most, cranial, population of NC is specified as gastrulation concludes and neurulation begins, while more posterior populations become specified as the body elongates. The mechanisms that govern development of the more posterior NC cells remain incompletely understood. Here, we report a key role for zebrafish Cdx4, a homeodomain transcription factor, in the development of posterior NC cells. We demonstrate that cdx4 is expressed in trunk NC cell progenitors, directly binds NC cell-specific enhancers in the NC GRN, and regulates expression of the key NC development gene foxd3 in the posterior body. Moreover, cdx4 mutants show disruptions to the segmental pattern of trunk NC cell migration due to loss of normal leader/follower cell dynamics. Finally, using cell transplantation to generate chimeric specimens, we show that Cdx4 does not function in the paraxial mesoderm-the environment adjacent to which crest migrates-to influence migratory behaviors. We conclude that cdx4 plays a critical, and likely tissue autonomous, role in the establishment of trunk NC migratory behaviors. Together, our results indicate that cdx4 functions as an early NC specifier gene in the posterior body of zebrafish embryos.

Keywords: Cdx4; Foxd3; Neural crest; Tailbud; Zebrafish.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Morphogenesis / genetics
  • Neural Crest / metabolism*
  • Neural Plate / metabolism
  • Neural Tube / metabolism
  • Neurulation / genetics
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism


  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Transcription Factors
  • Zebrafish Proteins
  • cdx4 protein, zebrafish
  • foxd3 protein, zebrafish