Multi-nucleation in two-cell human embryos stems from spindle and metaphase plate incoherence in the first mitosis
Pieper, G. H.; Aboelenain, M.; Munro, L.; Mihalas, B. P.; Currie, C. E.; Taylor, D.; Collins, D. M.; Hartshorne, G. M.; McAinsh, A. D.; Anderson, R. A.; Marston, A. L.
Show abstract
The first embryonic division in humans is highly error-prone and a source of aneuploidies. Multi-nucleation is prevalent in two-cell human embryos, with unknown cause. Here, we live-image human zygotes to elucidate the features of the first mitosis that predispose embryos to multinucleation. We show that failure to collect chromosomes into a single mass and establish a bipolar spindle during zygotic metaphase leads to severe multi-nucleation. We find that KIF10/CENP-E kinesin activity is essential to prevent the formation of multiple spindle poles and to congress chromosomes onto a metaphase plate. Furthermore, although the spindle assembly checkpoint mediates a delay in response to a highly disorganised spindle, KIF10/CENP-E-inhibited embryos ultimately undergo the first mitosis with a chaotic anaphase. Therefore, defective chromosome congression in the zygote combined with a failure to sense this error cause multi-nucleation. Remarkably, multi-nucleation can be corrected during the second mitotic division in a KIF10/CENP-E-dependent manner. We suggest that multi-nucleation may be a safeguarding mechanism to prevent chromosome loss during the highly error-prone first embryonic mitosis.
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