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Cell Stem Cell. 2015 Jun 4;16(6):639-52. doi: 10.1016/j.stem.2015.03.008. Epub 2015 Apr 23.

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

Author information

1
The Danish Stem Cell Centre (DanStem), University of Copenhagen, 2200 Copenhagen N, Denmark; Lund Stem Cell Center, Faculty of Medicine, Lund University, 22100 Lund, Sweden.
2
The Danish Stem Cell Centre (DanStem), University of Copenhagen, 2200 Copenhagen N, Denmark.
3
Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, Copenhagen Biocenter, 2200 Copenhagen N, Denmark.
4
Lund Stem Cell Center, Faculty of Medicine, Lund University, 22100 Lund, Sweden.
5
Department of Stem Cell Biology, Novo Nordisk A/S, 2760 Maaloev, Denmark.
6
The Danish Stem Cell Centre (DanStem), University of Copenhagen, 2200 Copenhagen N, Denmark; Lund Stem Cell Center, Faculty of Medicine, Lund University, 22100 Lund, Sweden. Electronic address: semb@sund.ku.dk.

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.

PMID:
25921273
DOI:
10.1016/j.stem.2015.03.008
[Indexed for MEDLINE]
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