Parental genome unification is highly error-prone in mammalian embryos
| Autor: | Patrick Aldag, Martyn Blayney, Melina Schuh, Andrea Lucas-Hahn, Jonas Bucevičius, Tommaso Cavazza, Clara Baker, M. Aushev, Antonio Z. Politi, Yuko Takeda, Meenakshi Choudhary, Heiner Niemann, Mary Herbert, Kay Elder, Gražvydas Lukinavičius |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Zygote chromosome segregation Embryonic Development Mitosis Aneuploidy Biology Microtubules Genome Article Chromosomes General Biochemistry Genetics and Molecular Biology Chromosome segregation 03 medical and health sciences 0302 clinical medicine nuclear pore complex medicine Animals Humans genome organization aneuploidy centrosomes 030304 developmental biology Cell Nucleus Centrosome Genetics 0303 health sciences dynein Pronucleus spindle Embryo Mammalian medicine.disease human embryo Spermatozoa fertilization embryonic structures Oocytes Cattle Ploidy Cell Nucleolus 030217 neurology & neurosurgery |
| Zdroj: | Cell |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2021.04.013 |
| Popis: | Summary 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. Graphical abstract Highlights • The parental genomes cluster at the pronuclear interface in human and bovine zygotes • Clustering is driven by centrosomes, which often reside at the pronuclear interface • Dynein orients chromosomes toward centrosomes via nuclear pore complexes as adaptors • Clustering defects lead to aneuploidy and micronuclei, impairing embryo development In human and bovine zygotes, parental genomes cluster and polarize toward each other in a highly error-prone process driven by centrosomes, dynein, microtubules, and nuclear pore complexes. Failure to cluster the parental genomes leads to chromosome segregation errors and micronuclei, which are incompatible with healthy embryo development. |
| Databáze: | OpenAIRE |
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