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Suppression of Fgf2 by ETS2 repressor factor (ERF) is required for chorionic trophoblast differentiation
Author(s) -
Vorgia Elena,
Zaragkoulias Andreas,
Peraki Ioanna,
Mavrothalassitis George
Publication year - 2017
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.22780
Subject(s) - biology , trophoblast , microbiology and biotechnology , transcription factor , fibroblast growth factor , cellular differentiation , repressor , placenta , genetics , gene , receptor , pregnancy , fetus
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, FGF 2 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.