p53 Suppresses Tetraploid Development in Mice

被引：28

作者：

Horii, Takuro ^{[1
]}

Yamamoto, Masamichi ^{[2
]}

Morita, Sumiyo ^{[1
]}

Kimura, Mika ^{[1
]}

Nagao, Yasumitsu ^{[3
]}

Hatada, Izuho ^{[1
]}

机构：

[1] Gunma Univ, Biosignal Genome Resource Ctr, Inst Mol & Cellular Regulat, Lab Genome Sci, 3-39-15 Showa Machi, Maebashi, Gunma 3718512, Japan

[2] Gunma Univ, Adv Sci Res Leaders Dev Unit, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan

[3] Jichi Med Univ, Med Res Ctr, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

关键词：

EMBRYONIC STEM-CELLS; CYTOKINESIS FAILURE; MAMMALIAN-CELLS; GENE-EXPRESSION; CYTOCHALASIN B; DNA-DAMAGE; MOUSE; APOPTOSIS; DIFFERENTIATION; RESPONSES;

D O I：

10.1038/srep08907

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

共 46 条

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