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Updated: Jul 31, 2025

Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis
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Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis

Published on: November 8, 2024

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The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate

Andreas Lackner1, Michael Müller1, Magdalena Gamperl1

  • 1Center for Anatomy and Cell Biology, Medical University of Vienna, A-1090, Vienna, Austria.

Nature Communications
|May 3, 2023
PubMed

Insights

Fibroblast growth factor (Fgf) signaling controls placental development. The Ets2 repressor factor (Erf) recruits the Nuclear Receptor Co-Repressor (NCoR1/2) complex to genes, repressing transcription and guiding trophoblast stem cell (TSC) differentiation.

Area of Science:

  • Developmental Biology
  • Epigenetics
  • Molecular Biology

Background:

  • Placental development involves complex cell fate decisions driven by signaling pathways.
  • Mechanisms translating signaling inputs into gene repression and lineage specification remain poorly understood.

Purpose of the Study:

  • To elucidate how signaling cues are converted into repressive mechanisms controlling trophoblast stem cell (TSC) differentiation.
  • To investigate the role of the Ets2 repressor factor (Erf) and Nuclear Receptor Co-Repressor (NCoR1/2) complex in placental development.

Main Methods:

  • Utilized mouse trophoblast stem cells (TSCs) with Fgf/Erk pathway inhibition.
  • Investigated Erf interaction with NCoR1/2 complex using genetic ablation of Erf and Tbl1x.
  • Analyzed gene expression and enhancer activity (H3K27ac) of target genes.

Main Results:

  • Inhibition of Fgf/Erk pathway in TSCs promotes Erf interaction with NCoR1/2.
  • Genetic disruption of Erf or Tbl1x impairs Erf/NCoR1/2 interaction and leads to TSC differentiation defects.
  • Erf recruits NCoR1/2 to silence target genes by decommissioning H3K27ac-marked enhancers.

Conclusions:

  • The Fgf/Erf/NCoR1/2 axis is a critical repressive mechanism governing TSC fate and placental development.
  • This pathway provides a model for understanding Fibroblast growth factor (Fgf)-mediated transcriptional control during development.

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