P53 suppresses tetraploid development in mice.

Takuro Horii,Sumiyo Morita,Izuho Hatada,Yasumitsu Nagao,Mika Kimura,Masamichi Yamamoto

doi:10.1038/srep08907

Takuro Horii, Sumiyo Morita + Show 4 more

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https://doi.org/10.1038/srep08907

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Journal: Scientific Reports	Publication Date: Mar 10, 2015
Citations: 31	License type: CC BY 4.0

Affiliation: Gunma University, Jichi Medical University

Abstract

Mammalian tetraploid embryos die in early development because of defects in the epiblast. Experiments with diploid/tetraploid chimeric mice, obtained via the aggregation of embryonic stem cells, clarified that while tetraploid cells are excluded from epiblast derivatives, diploid embryos with tetraploid extraembryonic tissues can develop to term. Today, this method, known as tetraploid complementation, is usually used for rescuing extraembryonic defects or for obtaining completely embryonic stem (ES) cell-derived pups. However, it is still unknown why defects occur in the epiblast during mammalian development. Here, we demonstrated that downregulation of p53, a tumour suppressor protein, rescued tetraploid development in the mammalian epiblast. Tetraploidy in differentiating epiblast cells triggered p53-dependent cell-cycle arrest and apoptosis, suggesting the activation of a tetraploidy checkpoint during early development. Finally, we found that p53 downregulation rescued tetraploid embryos later in gestation.

Highlights

Mammalian tetraploid embryos die in early development because of defects in the epiblast
Experiments with diploid/tetraploid chimeric mice, obtained via the aggregation of embryonic stem cells, clarified that while tetraploid cells are excluded from epiblast derivatives, diploid embryos with tetraploid extraembryonic tissues can develop to term
To determine the events that occurred during the development of tetraploid inner cell mass (ICM)-derived embryonic cells, tetraploid embryonic stem (ES) cell lines derived from the ICM of tetraploid blastocysts were established as the differentiation of ES cells into embryoid bodies (EBs) in vitro mimics events that occur during postimplantation

Summary

Introduction

Mammalian tetraploid embryos die in early development because of defects in the epiblast. Experiments with diploid/tetraploid chimeric mice, obtained via the aggregation of embryonic stem cells, clarified that while tetraploid cells are excluded from epiblast derivatives, diploid embryos with tetraploid extraembryonic tissues can develop to term Today, this method, known as tetraploid complementation, is usually used for rescuing extraembryonic defects or for obtaining completely embryonic stem (ES) cell-derived pups. Experiments with diploid/tetraploid aggregation chimeric mice clarified that while tetraploid cells are excluded from the epiblast derivatives of mid-gestation embryos[8,13,14], diploid embryos with tetraploid extraembryonic tissues can develop to term Today, this method, known as tetraploid complementation, is usually used for rescuing extraembryonic defects[15] or for obtaining completely embryonic stem (ES) cell-derived pups. We demonstrate that p53, a tumour suppressor protein, suppresses tetraploid development in mice

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