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http://purl.uniprot.org/citations/27870307http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27870307http://www.w3.org/2000/01/rdf-schema#comment"Gap junctional intercellular communication (GJIC) has been suggested to be involved in early embryonic development but the actual functional role remained elusive. Connexin (Cx) 43 and Cx45 are co-expressed in embryonic stem (ES) cells, form gap junctions and are considered to exhibit adhesive function and/or to contribute to the establishment of defined communication compartments. Here, we describe the generation of Cx43/Cx45-double deficient mouse ES cells to achieve almost complete breakdown of GJIC. Cre-loxP induced deletion of both, Cx43 and Cx45, results in a block of differentiation in embryoid bodies (EBs) without affecting pluripotency marker expression and proliferation in ES cells. We demonstrate that GJIC-incompetent ES cells fail to form primitive endoderm in EB cultures, representing the inductive key step of further differentiation events. Lentiviral overexpression of either Cx43 or Cx45 in Cx43/45 mutants rescued the observed phenotype, confirming the specificity and indicating a partially redundant function of both connexins. Upon differentiation GJIC-incompetent ES cells exhibit a strikingly altered subcellular localization pattern of the transcription factor NFATc3. Control EBs exhibit significantly more activated NFATc3 in cellular nuclei than mutant EBs suggesting that Cx-mediated communication is needed for synchronized NFAT activation to induce orchestrated primitive endoderm formation. Moreover, pharmacological inhibition of NFATc3 activation by Cyclosporin A, a well-described inhibitor of calcineurin, phenocopies the loss of GJIC in control cells. Stem Cells 2017;35:859-871."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.org/dc/terms/identifier"doi:10.1002/stem.2545"xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Pfeifer A."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Egert A."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Gebhardt M."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Zimmermann K."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Edenhofer F."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Willecke K."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Schorle H."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Ergun S."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Worsdorfer P."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Bosen F."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Komla Kessie D."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Russ N."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/author"Sekaran T."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/name"Stem Cells"xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/pages"859-871"xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/title"Abrogation of Gap Junctional Communication in ES Cells Results in a Disruption of Primitive Endoderm Formation in Embryoid Bodies."xsd:string
http://purl.uniprot.org/citations/27870307http://purl.uniprot.org/core/volume"35"xsd:string
http://purl.uniprot.org/citations/27870307http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27870307
http://purl.uniprot.org/citations/27870307http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27870307
http://purl.uniprot.org/uniprot/#_A0A1W2P8A3-mappedCitation-27870307http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27870307
http://purl.uniprot.org/uniprot/#_A0A1W2P793-mappedCitation-27870307http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27870307