The absence of Prep1 causes p53-dependent apoptosis of mouse pluripotent epiblast cells - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Journal Articles Development (Cambridge, England) Year : 2010

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

Abstract

Disruption of mouse Prep1, which codes for a homeodomain transcription factor, leads to embryonic lethality during post-implantation 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.

Dates and versions

hal-02661473 , version 1 (30-05-2020)

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Luis C Fernandez-Diaz, Audrey Laurent, Sara Girasoli, Margherita Turco, Elena Longobardi, et al.. The absence of Prep1 causes p53-dependent apoptosis of mouse pluripotent epiblast cells. Development (Cambridge, England), 2010, 137 (20), pp.3393-3403. ⟨10.1242/dev.050567⟩. ⟨hal-02661473⟩

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