Autophagy-mediated apoptosis eliminates aneuploid cells in a mouse model of chromosome mosaicism

Shruti Singla, Lisa K. Iwamoto-Stohl, Meng Zhu and Magdalena Zernicka-Goetz ()
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Shruti Singla: University of Cambridge, Downing Street
Lisa K. Iwamoto-Stohl: University of Cambridge, Downing Street
Meng Zhu: University of Cambridge, Downing Street
Magdalena Zernicka-Goetz: University of Cambridge, Downing Street

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract The high incidence of aneuploidy in the embryo is considered the principal cause for low human fecundity. However, the prevalence of aneuploidy dramatically declines as pregnancy progresses, with the steepest drop occurring as the embryo completes implantation. Despite the fact that the plasticity of the embryo in dealing with aneuploidy is fundamental to normal development, the mechanisms responsible for eliminating aneuploid cells are unclear. Here, using a mouse model of chromosome mosaicism, we show that aneuploid cells are preferentially eliminated from the embryonic lineage in a p53-dependent process involving both autophagy and apoptosis before, during and after implantation. Moreover, we show that diploid cells in mosaic embryos undertake compensatory proliferation during the implantation stages to confer embryonic viability. Together, our results indicate a close link between aneuploidy, autophagy, and apoptosis to refine the embryonic cell population and ensure only chromosomally fit cells proceed through development of the fetus.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16796-3

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DOI: 10.1038/s41467-020-16796-3

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