| http://purl.uniprot.org/citations/22573616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22573616 | http://www.w3.org/2000/01/rdf-schema#comment | "The canonical Wnt/β-catenin signaling pathway classically functions through the activation of target genes by Tcf/Lef-β-catenin complexes. In contrast to β-catenin-dependent functions described for Tcf1, Tcf4 and Lef1, the known embryonic functions for Tcf3 in mice, frogs and fish are consistent with β-catenin-independent repressor activity. In this study, we genetically define Tcf3-β-catenin functions in mice by generating a Tcf3ΔN knock-in mutation that specifically ablates Tcf3-β-catenin. Mouse embryos homozygous for the knock-in mutation (Tcf3(ΔN/ΔN)) progress through gastrulation without apparent defects, thus genetically proving that Tcf3 function during gastrulation is independent of β-catenin interaction. Tcf3(ΔN/ΔN) mice were not viable, and several post-gastrulation defects revealed the first in vivo functions of Tcf3-β-catenin interaction affecting limb development, vascular integrity, neural tube closure and eyelid closure. Interestingly, the etiology of defects indicated an indirect role for Tcf3-β-catenin in the activation of target genes. Tcf3 directly represses transcription of Lef1, which is stimulated by Wnt/β-catenin activity. These genetic data indicate that Tcf3-β-catenin is not necessary to activate target genes directly. Instead, our findings support the existence of a regulatory circuit whereby Wnt/β-catenin counteracts Tcf3 repression of Lef1, which subsequently activates target gene expression via Lef1-β-catenin complexes. We propose that the Tcf/Lef circuit model provides a mechanism downstream of β-catenin stability for controlling the strength of Wnt signaling activity during embryonic development."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.org/dc/terms/identifier | "doi:10.1242/dev.076067"xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/author | "Nguyen H."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/author | "Fuchs E."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/author | "Wu C.I."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/author | "Merrill B.J."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/author | "Hoffman J.A."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/author | "Ford E.M."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/author | "Shy B.R."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/name | "Development"xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/pages | "2118-2129"xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/title | "Function of Wnt/beta-catenin in counteracting Tcf3 repression through the Tcf3-beta-catenin interaction."xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://purl.uniprot.org/core/volume | "139"xsd:string |
| http://purl.uniprot.org/citations/22573616 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22573616 |
| http://purl.uniprot.org/citations/22573616 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22573616 |
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| http://purl.uniprot.org/uniprot/#_A0A0A6YVX7-mappedCitation-22573616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22573616 |
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| http://purl.uniprot.org/uniprot/#_E9Q990-mappedCitation-22573616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22573616 |
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| http://purl.uniprot.org/uniprot/#_D3Z1Z4-mappedCitation-22573616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22573616 |