The absence of Prep1 causes p53-dependent apoptosis of mouse pluripotent epiblast cells

Luis C. Fernandez-Diaz, Audrey Laurent, Sara Girasoli, Margherita Turco, Elena Longobardi, Giorgio Iotti, Nancy A. Jenkins, Maria Teresa Fiorenza, Neal G. Copeland, Francesco Blasi

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Disruption of mouse Prep1, which codes for a homeodomain transcription factor, leads to embryonic lethality during postimplantation stages. Prep1 -/- embryos stop developing after implantation and before anterior visceral endoderm (AVE) formation. In Prep1-/- embryos at E6.5 (onset of gastrulation), the AVE is absent and the proliferating extra-embryonic ectoderm and epiblast, marked by Bmp4 and Oct4, respectively, are reduced in size. At E.7.5, Prep1-/- embryos are small and very delayed, showing no evidence of primitive streak or of differentiated embryonic lineages. Bmp4 is expressed residually, while the reduced number of Oct4-positive cells is constant up to E8.5. At E6.5, Prep1-/- embryos retain a normal mitotic index but show a major increase in cleaved caspase 3 and TUNEL staining, indicating apoptosis. Therefore, the mouse embryo requires Prep1 when undergoing maximal expansion in cell number. Indeed, the phenotype is partially rescued in a p53-/-, but not in a p16-/-, background. Apoptosis is probably due to DNA damage as Atm downregulation exacerbates the phenotype. Despite this early lethal phenotype, Prep1 is not essential for ES cell establishment. A differential embryonic expression pattern underscores the unique function of Prep1 within the Meis-Prep family.

Original languageEnglish (US)
Pages (from-to)3393-3403
Number of pages11
JournalDevelopment
Volume137
Issue number20
DOIs
StatePublished - Oct 15 2010

Keywords

  • Embryo development
  • Epiblast
  • Gastrulation
  • Mouse
  • p53 (trp53)
  • Prep1 (Pknox1)

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

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