p53 suppresses tetraploid development in mice

Scientific Reports
Takuro HoriiIzuho Hatada

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.

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Citations

Aug 30, 2016·The Journal of Reproduction and Development·Hiroyuki ImaiKiyoshi Kano
Aug 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Teresa OlbrichOscar Fernandez-Capetillo
Aug 10, 2018·The Journal of Veterinary Medical Science·Hiroyuki ImaiKiyoshi Kano
Mar 11, 2020·Zygote : the Biology of Gametes and Early Embryos·Hiroyuki ImaiKiyoshi Kano
Jun 25, 2019·Communications Biology·Kathleen M BroughtonMark A Sussman
Oct 28, 2019·Nature Communications·Lia Mara Gomes Paim, Greg FitzHarris
Jun 18, 2020·Frontiers in Cell and Developmental Biology·Georgia R Kafer, Anthony J Cesare
Aug 12, 2020·Nature Reviews. Genetics·Nicholas E Baker
Aug 18, 2016·The Journal of Biological Chemistry·Wataru YamazakiManabu Kawahara
Jan 12, 2020·Communications Biology·Kathleen M BroughtonMark A Sussman
Mar 25, 2021·Cell Reports·Akshay NarkarRong Li
Apr 17, 2021·Genes & Development·Steven PilleyKaren H Vousden
Aug 7, 2021·DNA Repair·Mumingjiang Munisha, John C Schimenti
Sep 8, 2021·Reproduction, Fertility, and Development·Dawid WiniarczykJacek Andrzej Modli Ski

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Methods Mentioned

BETA
fluorescence activated cell sorting
Assay
electrophoresis
PCR
genotyping

Software Mentioned

Image J

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