Loading...
p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification.
Pieters, Tim Goossens, Steven Haenebalcke, Lieven Andries, Vanessa Stryjewska, Agata De Rycke, Riet Lemeire, Kelly Hochepied, Tino Huylebroeck, Danny Berx, Geert
Pieters, Tim
Goossens, Steven
Haenebalcke, Lieven
Andries, Vanessa
Stryjewska, Agata
De Rycke, Riet
Lemeire, Kelly
Hochepied, Tino
Huylebroeck, Danny
Berx, Geert
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2016-08
Submitted date
Files
Loading...
Open Access publication
Adobe PDF, 23.72 MB
Loading...
supporting figure S1
Adobe PDF, 435.45 KB
Loading...
supporting figure S2
Adobe PDF, 2.77 MB
Loading...
supporting figure S3
Adobe PDF, 522.85 KB
Loading...
supporting figure S4
Adobe PDF, 3.64 MB
Other Titles
Abstract
E-cadherin-mediated cell-cell adhesion is critical for naive pluripotency of cultured mouse embryonic stem cells (mESCs). E-cadherin-depleted mESC fail to downregulate their pluripotency program and are unable to initiate lineage commitment. To further explore the roles of cell adhesion molecules during mESC differentiation, we focused on p120 catenin (p120ctn). Although one key function of p120ctn is to stabilize and regulate cadherin-mediated cell-cell adhesion, it has many additional functions, including regulation of transcription and Rho GTPase activity. Here, we investigated the role of mouse p120ctn in early embryogenesis, mESC pluripotency and early fate determination. In contrast to the E-cadherin-null phenotype, p120ctn-null mESCs remained pluripotent, but their in vitro differentiation was incomplete. In particular, they failed to form cystic embryoid bodies and showed defects in primitive endoderm formation. To pinpoint the underlying mechanism, we undertook a structure-function approach. Rescue of p120ctn-null mESCs with different p120ctn wild-type and mutant expression constructs revealed that the long N-terminal domain of p120ctn and its regulatory domain for RhoA were dispensable, whereas its armadillo domain and interaction with E-cadherin were crucial for primitive endoderm formation. We conclude that p120ctn is not only an adaptor and regulator of E-cadherin, but is also indispensable for proper lineage commitment.
Citation
p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification. 2016, 12 (8):e1006243 PLoS Genet.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1553-7404