Canonical Wnt Signaling and Its Antagonist Regulate Anterior-Posterior Axis Polarization by Guiding Cell Migration in Mouse Visceral Endoderm

Dev Cell. 2005 Nov;9(5):639-50. doi: 10.1016/j.devcel.2005.09.011.

Abstract

The mouse embryonic axis is initially formed with a proximal-distal orientation followed by subsequent conversion to a prospective anterior-posterior (A-P) polarity with directional migration of visceral endoderm cells. Importantly, Otx2, a homeobox gene, is essential to this developmental process. However, the genetic regulatory mechanism governing axis conversion is poorly understood. Here, defective axis conversion due to Otx2 deficiency can be rescued by expression of Dkk1, a Wnt antagonist, or following removal of one copy of the beta-catenin gene. Misexpression of a canonical Wnt ligand can also inhibit correct A-P axis rotation. Moreover, asymmetrical distribution of beta-catenin localization is impaired in the Otx2-deficient and Wnt-misexpressing visceral endoderm. Concurrently, canonical Wnt and Dkk1 function as repulsive and attractive guidance cues, respectively, in the migration of visceral endoderm cells. We propose that Wnt/beta-catenin signaling mediates A-P axis polarization by guiding cell migration toward the prospective anterior in the pregastrula mouse embryo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Body Patterning / physiology*
  • Cell Movement / physiology
  • Embryonic Development / genetics
  • Embryonic Development / physiology
  • Endoderm / cytology
  • Endoderm / physiology*
  • Gene Expression Regulation, Developmental / physiology
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Biological
  • Otx Transcription Factors / genetics*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Viscera / cytology
  • Viscera / embryology
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / genetics
  • Wnt Proteins / physiology*
  • beta Catenin / genetics
  • beta Catenin / physiology

Substances

  • Dkk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Otx Transcription Factors
  • Wnt Proteins
  • Wnt8a protein, mouse
  • beta Catenin