Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells

Tiziana Parisi, Andreas R. Beck, Nathalie Rougier, Tom McNeil, Linda Lucian, Zena Werb, Bruno Amati

Research output: Contribution to journalArticle

Abstract

In mammalian cells, cyclin E-CDK2 complexes are activated in the late G1 phase of the cell cycle and are believed to have an essential role in promoting S-phase entry. We have targeted the murine genes CCNE1 and CCNE2, encoding cyclins E1 and E2. Whereas single knockout mice were viable, double knockout embryos died around midgestation. Strikingly, however, these embryos showed no overt defects in cell proliferation. Instead, we observed developmental phenotypes consistent with placental dysfunction. Mutant placentas had an overall normal structure, but the nuclei of trophoblast giant cells, which normally undergo endoreplication and reach elevated ploidies, showed a marked reduction in DNA content. We derived trophoblast stem cells from double knockout E3.5 blastocysts. These cells retained the ability to differentiate into giant cells in vitro, but were unable to undergo multiple rounds of DNA synthesis, demonstrating that the lack of endoreplication was a cell-autonomous defect. Thus, during embryonic development, the needs for E-type cyclins can be overcome in mitotic cycles but not in endoreplicating cells.

Original languageEnglish
Pages (from-to)4794-4803
Number of pages10
JournalEMBO Journal
Volume22
Issue number18
DOIs
Publication statusPublished - Sep 15 2003

Keywords

  • Cell cycle
  • Cyclin E
  • Endoreplication
  • Placenta
  • Trophoblast

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Parisi, T., Beck, A. R., Rougier, N., McNeil, T., Lucian, L., Werb, Z., & Amati, B. (2003). Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells. EMBO Journal, 22(18), 4794-4803. https://doi.org/10.1093/emboj/cdg482