β-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4.

Research output: Contribution to journalArticle

Abstract

Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector β-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we demonstrate a broader role for β-catenin in PS formation by analyzing its genome-wide binding in a human embryonic stem cell model of PS induction. β-catenin occupies regulatory regions in numerous PS and neural crest genes, and direct interactions between β-catenin and the Nodal effectors SMAD2/SMAD3 are required at these regions for PS gene activation. Furthermore, OCT4 binding in proximity to these sites is likewise required for PS induction, suggesting a collaborative interaction between β-catenin and OCT4. Induction of neural crest genes by β-catenin is repressed by SMAD2/SMAD3, ensuring proper lineage specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions.

Details

Authors
  • Nina Funa
  • Karen Schachter
  • Mads Lerdrup
  • Jenny Ekberg
  • Katja Hess
  • Nikolaj Dietrich
  • Christian Honoré
  • Klaus Hansen
  • Henrik Semb
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology
Original languageEnglish
Pages (from-to)639-652
JournalCell Stem Cell
Volume16
Issue number6
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes