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Pré-Publication, Document De Travail Année : 2022

Ectopic activation of the polar body extrusion pathway triggers cell fragmentation in preimplantation embryos

Résumé

Abstract Cell fragmentation occurs during physiological processes, such as apoptosis, migration, or germ cell development. Fragmentation is also commonly observed during preimplantation development of human embryos and is associated with poor implantation prognosis during Assisted Reproductive Technology (ART) procedures. Despite its biological and clinical relevance, the mechanisms leading to cell fragmentation are unclear. Light sheet microscopy imaging of mouse embryos reveals that compromised spindle anchoring, due to Myo1c knockout or dynein inhibition, leads to fragmentation. We further show that defective spindle anchoring brings DNA in close proximity to the cell cortex, which, in stark contrast to previous reports in mitotic cells, locally triggers actomyosin contractility and pinches off cell fragments. The activation of actomyosin contractility by DNA in preimplantation embryos is reminiscent of the signals mediated by small GTPases throughout polar body extrusion (PBE) during meiosis. By interfering with the signals driving PBE, we find that this meiotic signaling pathway remains active during cleavage stages and is both required and sufficient to trigger fragmentation. Together, we find that fragmentation happens in mitosis after ectopic activation of actomyosin contractility by signals emanating from DNA, similar to those observed during meiosis. Our study uncovers the mechanisms underlying fragmentation in preimplantation embryos and, more generally, offers insight into the regulation of mitosis during the maternal-zygotic transition.
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hal-04243755 , version 1 (16-10-2023)

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Diane Pelzer, Ludmilla de Plater, Peta Bradbury, Adrien Eichmuller, Anne Bourdais, et al.. Ectopic activation of the polar body extrusion pathway triggers cell fragmentation in preimplantation embryos. 2023. ⟨hal-04243755⟩
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