title: Suppression of Fgf2 by ETS2 repressor factor (ERF) is required for chorionic trophoblast differentiation.
abstract: ETS2 repressor factor (ERF) is a ubiquitous transcriptional repressor regulated by Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Homozygous deletion of Erf in mice blocks chorionic trophoblast differentiation, resulting in the failure of chorioallantoic fusion and subsequent embryo death. Fibroblast growth factor (FGF) signaling is important for proper trophoblast stem cell (TSC) differentiation and development of the hemochorial placenta. Lack of Fgf2 promotes TSC differentiation, while FGF4 or FGF2 is required for murine TSC maintenance. Here, we show that low in vivo Fgf2 mRNA abundance occurs in patches of placental chorion cells and ex vivo in TSCs. This expression is repressed via direct interaction of ERF with the Fgf2 transcription unit is increased in the absence of ERF, and is decreased in the presence of an ERF mutant resistant to ERK phosphorylation. Thus, FGF2 inhibition by ERF appears to be necessary for proper chorionic TSC differentiation, and may account for the block of chorionic trophoblast differentiation in Erf-knockout animals. The differentiation of ERF-overexpressing TSC lines also suggests that ERF may have an FGF2-independent effect during the commitment towards syncytiotrophoblasts.
authors.affiliation: Medical School, University of Crete, Heraklion, Crete, Greece.|IMBB, FORTH, Heraklion, Crete, Greece.
authors.forename: Elena
authors.initials: E
authors.lastname: Vorgia
authors.affiliation: Medical School, University of Crete, Heraklion, Crete, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zaragkoulias
authors.affiliation: Medical School, University of Crete, Heraklion, Crete, Greece.|IMBB, FORTH, Heraklion, Crete, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Peraki
authors.affiliation: Medical School, University of Crete, Heraklion, Crete, Greece.|IMBB, FORTH, Heraklion, Crete, Greece.
authors.forename: George
authors.identifier: 0000-0001-6214-3179
authors.initials: G
authors.lastname: Mavrothalassitis
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002823:Chorion / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D051519:Fibroblast Growth Factor 4 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D050787:Proto-Oncogene Protein c-ets-2 / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: C494070:Ets2 protein, mouse; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D050787:Proto-Oncogene Protein c-ets-2; D016222:Fibroblast Growth Factor 2; D048052:Mitogen-Activated Protein Kinase 3
keywords: placenta; syncytiotrophoblast; transcriptional repression