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

På svenska

Author

  • Nina Funa
  • Karen Schachter
  • Mads Lerdrup
  • Jenny Ekberg
  • Katja Hess
  • Nikolaj Dietrich
  • Christian Honoré
  • Klaus Hansen
  • Henrik Semb

Summary, in English

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.

Publishing year

2015

Language

English

Pages

639-652

Publication/Series

Cell Stem Cell

Volume

16

Issue

6

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1934-5909