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

Funa, Nina LU ; Schachter, Karen LU ; Lerdrup, Mads; Ekberg, Jenny LU ; Hess, Katja LU ; Dietrich, Nikolaj; Honoré, Christian; Hansen, Klaus and Semb, Henrik LU (2015) In Cell Stem Cell 16(6). p.639-652
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Stem Cell
volume
16
issue
6
pages
639 - 652
publisher
Cell Press
external identifiers
  • pmid:25921273
  • wos:000355932300013
  • scopus:84955406207
ISSN
1934-5909
DOI
10.1016/j.stem.2015.03.008
language
English
LU publication?
yes
id
ec0916cb-6d61-44b9-b598-927da6bc0bbf (old id 5461893)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25921273?dopt=Abstract
date added to LUP
2015-06-03 08:38:56
date last changed
2017-11-19 03:19:40
@article{ec0916cb-6d61-44b9-b598-927da6bc0bbf,
  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.},
  author       = {Funa, Nina and Schachter, Karen and Lerdrup, Mads and Ekberg, Jenny and Hess, Katja and Dietrich, Nikolaj and Honoré, Christian and Hansen, Klaus and Semb, Henrik},
  issn         = {1934-5909},
  language     = {eng},
  number       = {6},
  pages        = {639--652},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {β-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4.},
  url          = {http://dx.doi.org/10.1016/j.stem.2015.03.008},
  volume       = {16},
  year         = {2015},
}