Tetraploidy causes chromosomal instability in acentriolar mouse embryos

Lia Mara Gomes Paim and Greg FitzHarris ()
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Lia Mara Gomes Paim: Centre de Recherche du Centre Hospitalier de l’Université de Montréal
Greg FitzHarris: Centre de Recherche du Centre Hospitalier de l’Université de Montréal

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Tetraploidisation is considered a common event in the evolution of chromosomal instability (CIN) in cancer cells. The current model for how tetraploidy drives CIN in mammalian cells is that a doubling of the number of centrioles that accompany the genome doubling event leads to multipolar spindle formation and chromosome segregation errors. By exploiting the unusual scenario of mouse blastomeres, which lack centrioles until the ~64-cell stage, we show that tetraploidy can drive CIN by an entirely distinct mechanism. Tetraploid blastomeres assemble bipolar spindles dictated by microtubule organising centres, and multipolar spindles are rare. Rather, kinetochore-microtubule turnover is altered, leading to microtubule attachment defects and anaphase chromosome segregation errors. The resulting blastomeres become chromosomally unstable and exhibit a dramatic increase in whole chromosome aneuploidies. Our results thus reveal an unexpected mechanism by which tetraploidy drives CIN, in which the acquisition of chromosomally-unstable microtubule dynamics contributes to chromosome segregation errors following tetraploidisation.

Date: 2019
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DOI: 10.1038/s41467-019-12772-8

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