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Parental genome unification is highly error-prone in mammalian embryos

Lookup NU author(s): Dr Yuko Takeda, Dr Magomet Aushev, Dr Meenakshi Choudhary, Professor Mary Herbert

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2021 The AuthorsMost human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but its origin remains elusive. Human zygotes that cluster their nucleoli at the pronuclear interface are thought to be more likely to develop into healthy euploid embryos. Here, we show that the parental genomes cluster with nucleoli in each pronucleus within human and bovine zygotes, and clustering is required for the reliable unification of the parental genomes after fertilization. During migration of intact pronuclei, the parental genomes polarize toward each other in a process driven by centrosomes, dynein, microtubules, and nuclear pore complexes. The maternal and paternal chromosomes eventually cluster at the pronuclear interface, in direct proximity to each other, yet separated. Parental genome clustering ensures the rapid unification of the parental genomes on nuclear envelope breakdown. However, clustering often fails, leading to chromosome segregation errors and micronuclei, incompatible with healthy embryo development.


Publication metadata

Author(s): Cavazza T, Takeda Y, Politi AZ, Aushev M, Aldag P, Baker C, Choudhary M, Bucevicius J, Lukinavicius G, Elder K, Blayney M, Lucas-Hahn A, Niemann H, Herbert M, Schuh M

Publication type: Article

Publication status: Published

Journal: Cell

Year: 2021

Volume: 184

Issue: 11

Pages: 2860-2877.e22

Online publication date: 07/05/2021

Acceptance date: 08/04/2021

Date deposited: 11/06/2021

ISSN (print): 0092-8674

ISSN (electronic): 1097-4172

Publisher: Elsevier B.V.

URL: https://doi.org/10.1016/j.cell.2021.04.013

DOI: 10.1016/j.cell.2021.04.013

PubMed id: 33964210


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