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dc.contributor.authorPieters, Tim
dc.contributor.authorGoossens, Steven
dc.contributor.authorHaenebalcke, Lieven
dc.contributor.authorAndries, Vanessa
dc.contributor.authorStryjewska, Agata
dc.contributor.authorDe Rycke, Riet
dc.contributor.authorLemeire, Kelly
dc.contributor.authorHochepied, Tino
dc.contributor.authorHuylebroeck, Danny
dc.contributor.authorBerx, Geert
dc.contributor.authorStemmler, Marc P
dc.contributor.authorWirth, Dagmar
dc.contributor.authorHaigh, Jody J
dc.contributor.authorvan Hengel, Jolanda
dc.contributor.authorvan Roy, Frans
dc.date.accessioned2016-09-14T11:42:11Z
dc.date.available2016-09-14T11:42:11Z
dc.date.issued2016-08
dc.identifier.citationp120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification. 2016, 12 (8):e1006243 PLoS Genet.en
dc.identifier.issn1553-7404
dc.identifier.pmid27556156
dc.identifier.doi10.1371/journal.pgen.1006243
dc.identifier.urihttp://hdl.handle.net/10033/620136
dc.description.abstractE-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.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titlep120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection researchz, Inhoffenstr. 7, 38124 Braunschweig.en
dc.identifier.journalPLoS geneticsen
refterms.dateFOA2018-06-12T21:23:53Z
html.description.abstractE-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.


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