β-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5461893
- author
- Funa, Nina LU ; Schachter, Karen LU ; Lerdrup, Mads ; Ekberg, Jenny LU ; Hess, Katja LU ; Dietrich, Nikolaj ; Honoré, Christian ; Hansen, Klaus and Semb, Henrik LU
- organization
- publishing date
- 2015
- 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
- pmid:25921273
- 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
- 2016-04-01 10:56:47
- date last changed
- 2022-08-13 00:18:52
@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}}, doi = {{10.1016/j.stem.2015.03.008}}, volume = {{16}}, year = {{2015}}, }