title: Activation of the beta-catenin/Lef-Tcf pathway is obligate for formation of primitive endoderm by mouse F9 totipotent teratocarcinoma cells in response to retinoic acid.
abstract: The morphogen retinoic acid promotes the formation of primitive endoderm in mouse F9 teratocarcinoma cells as does the stimulation of the Frizzled-1 pathway. We investigated whether the beta-catenin/Lef-Tcf-sensitive transcriptional pathway activated by Frizzled-1 plays a role in the retinoic acid-induced pathway to primitive endoderm formation. An analysis of Lef-Tcf-sensitive transcription reveals increased transcription at 1 and 4 h post-treatment with retinoic acid. The stimulation of Lef-Tcf-sensitive transcription as well as the formation of primitive endoderm was accompanied by the stabilization of beta-catenin as observed in activation of the Frizzled-1 pathway. Transient transfection of F9 cells with an expression vector harboring a dominant-negative mutant of Tcf4 resulted in the attenuation of both the increase in Lef-Tcf-sensitive transcription and formation of primitive endoderm in response to the morphogen. Clones stably transfected to express the dominant-negative Tcf4 displayed a block in retinoic acid-induced activation of Lef-Tcf-sensitive transcription and primitive endoderm formation. These data reveal the obligate role of the beta-catenin/Lef-Tcf transcriptional pathway in the action of the morphogen retinoic acid.
authors.affiliation: Department of Pharmacology, Diabetes & Metabolic Diseases Research Center, State University of New York (SUNY) at Stony Brook, Stony Brook, NY 11794-8651, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Lee
authors.forename: Craig C
authors.initials: CC
authors.lastname: Malbon
authors.forename: Hsien-yu
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004707:Endoderm / Q000502:physiology*; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D051820:TCF Transcription Factors; D018243:Teratocarcinoma / Q000473:pathology*; D015534:Trans-Activators / Q000502:physiology*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin; D014212:Tretinoin