title: The transcription factor TCFAP2C/AP-2gamma cooperates with CDX2 to maintain trophectoderm formation.
abstract: In mammals, cell lineage specification is established at the blastocyst stage. At this stage, transcription factor Cdx2 represses pluripotency genes, thus promoting extraembryonic trophoblast fate. Recently, transcription factor Gata3 was shown to act in a parallel pathway in promoting trophoblast cell fate, suggesting that there are more factors working in the trophoblast lineage. Here, we report that the transcription factor Tcfap2c is expressed at a high level in the trophectoderm and is able to induce trophoblast fate in embryonic stem cells. Trophoblast fate induced by Tcfap2c does not require Cdx2 and vice versa, suggesting that the molecules act in alternative pathways. However, both Tcfap2c and Cdx2 are required for the upregulation of Elf5, a marker of trophoblast stem cell maintenance, suggesting that both factors are required for stable trophoblast induction. Tcfap2c-induced trophoblast-like cells are stable in long-term culture, indicating that they are capable of self-renewal. Tcfap2c-controlled trophoblast maintenance involves the induction of Cdx2 and the repression of the pluripotency factor Nanog. Tcfap2c-induced trophoblast-like cells differentiate to trophoblast derivatives in vitro and contribute to the trophectoderm in blastocysts in vivo. Taken together, these observations suggest that Tcfap2c and Cdx2 cooperate to override the pluripotency program and establish the extraembryonic trophoblast maintenance program in murine embryos.
authors.affiliation: Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Sigmund-Freud-Str. 25, Bonn D-53127, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kuckenberg
authors.forename: Sandra
authors.initials: S
authors.lastname: Buhl
authors.forename: Tatiana
authors.initials: T
authors.lastname: Woynecki
authors.forename: Betina
authors.initials: B
authors.lastname: van Fürden
authors.forename: Elena
authors.initials: E
authors.lastname: Tolkunova
authors.forename: Friederike
authors.initials: F
authors.lastname: Seiffe
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.forename: Alexey
authors.initials: A
authors.lastname: Tomilin
authors.forename: Elke
authors.initials: E
authors.lastname: Winterhager
authors.forename: Hubert
authors.initials: H
authors.lastname: Schorle
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D047108:Embryonic Development / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000071317:Nanog Homeobox Protein; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology
chemical_list: D015415:Biomarkers; D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; C583890:Tfap2c protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors
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