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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; ... van Roy, F; + view all (2016) p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification. PLoS Genetics , 12 (8) , Article e1006243. 10.1371/journal.pgen.1006243. Green open access

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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.

Type: Article
Title: p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1006243
Publisher version: https://doi.org/10.1371/journal.pgen.1006243
Language: English
Additional information: Copyright © 2016 Pieters et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Animals, Blastocyst, Cadherins, Catenins, Cell Adhesion, Cell Differentiation, Cell Lineage, Cell Polarity, Embryoid Bodies, Embryonic Development, Endoderm, Humans, Mice, Mouse Embryonic Stem Cells, Optical Imaging, Pluripotent Stem Cells, rhoA GTP-Binding Protein
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/1555122
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