Parental Genome Unification is Highly Error-prone in Mammalian Embryos

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2021 May 8

PMID 33964210

Citations 75

Authors

Tommaso Cavazza

Yuko Takeda

Antonio Z Politi

Magomet Aushev

Patrick Aldag

Clara Baker

Meenakshi Choudhary

Jonas Bucevicius

Grazvydas Lukinavicius

Kay Elder

Martyn Blayney

Andrea Lucas-Hahn

Heiner Niemann

Mary Herbert

Melina Schuh

Affiliations

Soon will be listed here.

Abstract

Most 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.

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