| First Author | Fernandez-Diaz LC | Year | 2010 |
| Journal | Development | Volume | 137 |
| Issue | 20 | Pages | 3393-403 |
| PubMed ID | 20826531 | Mgi Jnum | J:165811 |
| Mgi Id | MGI:4838491 | Doi | 10.1242/dev.050567 |
| Citation | Fernandez-Diaz LC, et al. (2010) The absence of Prep1 causes p53-dependent apoptosis of mouse pluripotent epiblast cells. Development 137(20):3393-403 |
| abstractText | 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. |
