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

Isao Matsuo,Shigenobu Yonemura,Yasuhisa Matsui,Kazuki Nakao,Shinichi Aizawa,Daiji Okamura,Hiroshi Nakano,Jose A Belo,Chiharu Kimura-Yoshida

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.

Highlights

By embryonic day 5.5 (E5.5), the mouse embryonic axis is initially generated in a proximal-distal (P-D) orientation; subsequently, prior to gastrulation, this axis is converted to the anterior-posterior (A-P) direction (Beddington and Robertson, 1999)
We propose that Wnt/ ␤-catenin signaling mediates A-P axis polarization by guiding cell migration toward the prospective anterior in the pregastrula mouse embryo
Expression of the Dkk1 Gene during distal visceral endoderm (DVE) Migration We previously demonstrated that Otx2−/− embryos fail to form the A-P axis correctly (Kimura et al, 2000)

Summary

Introduction

By embryonic day 5.5 (E5.5), the mouse embryonic axis is initially generated in a proximal-distal (P-D) orientation; subsequently, prior to gastrulation, this axis is converted to the anterior-posterior (A-P) direction (Beddington and Robertson, 1999). During the “axis rotation” process, a distinct population of visceral endoderm cells marked by Hex expression is located at the distal tip of the egg cylinder; these cells migrate proximally to the prospective anterior side of the embryo (Srinivas et al, 2004; Thomas et al, 1998). Axis conversion involves the coordination of both anterior migration of distal visceral endoderm (DVE) cells and the posterior shift of proximal markers, which transforms the P-D orientation to the definitive A-P polarity. TGF-β/ Nodal signaling promotes DVE formation; Nodal in the epiblast induces Nodal in the visceral endoderm as well as other target genes such as Otx and Nodal antagonists, e.g., Cerl and Lefty (Brennan et al, 2001). The Nodal antagonists Cerl and Lefty participate in the formation of anterior visceral endoderm (AVE) by controlling cell proliferation in the visceral endoderm layer (Yamamoto et al, 2004)

Results

Discussion

Conclusion