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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
β-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4.
Cell Stem Cell 16, 639-652 (2015)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
ISSN (print) / ISBN
1934-5909
e-ISSN
1875-9777
Zeitschrift
Cell Stem Cell
Quellenangaben
Band: 16,
Heft: 6,
Seiten: 639-652
Verlag
Elsevier
Verlagsort
Cambridge, Mass.
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Transl. Stem Cell Research (ITS)