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 language | English (US) |
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Pages (from-to) | 3393-3403 |
Number of pages | 11 |
Journal | Development |
Volume | 137 |
Issue number | 20 |
DOIs | |
State | Published - Oct 15 2010 |
Keywords
- Embryo development
- Epiblast
- Gastrulation
- Mouse
- p53 (trp53)
- Prep1 (Pknox1)
ASJC Scopus subject areas
- Developmental Biology
- Molecular Biology