p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification

Pieters T, Goossens S, Haenebalcke L, Andries V, Stryjewska A, De Rycke R, Lemeire K, Hochepied T, Huylebroeck D, Berx G, Stemmler M, Wirth D, Haigh JJ, Van Hengel J, Van Roy F (2016)

Publication Type: Journal article

Publication year: 2016

Journal

PLoS Genetics Public Library of Science

Book Volume: 12

Pages Range: e1006243

Journal Issue: 8

DOI: 10.1371/journal.pgen.1006243

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.

Authors with CRIS profile

Marc Stemmler Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung

Involved external institutions

Universiteit Gent (UGent) / Ghent University BE Belgium (BE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Monash University AU Australia (AU) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE)

How to cite

APA:

Pieters, T., Goossens, S., Haenebalcke, L., Andries, V., Stryjewska, A., De Rycke, R.,... Van Roy, F. (2016). p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification. PLoS Genetics, 12(8), e1006243. https://doi.org/10.1371/journal.pgen.1006243

MLA:

Pieters, Tim, et al. "p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification." PLoS Genetics 12.8 (2016): e1006243.

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