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  Parental genome unification is highly error-prone in mammalian embryos

Cavazza, T., Takeda, Y., Politi, A., Aushev, M., Aldag, P., Baker, C., et al. (2021). Parental genome unification is highly error-prone in mammalian embryos. Cell, 184(11), 2860-2877.e22. doi:10.1016/j.cell.2021.04.013.

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 Creators:
Cavazza, T.1, Author              
Takeda, Y., Author
Politi, A.2, Author              
Aushev, M., Author
Aldag, P., Author
Baker, C., Author
Choudhary, M., Author
Bucevičius, J.3, Author              
Lukinavičius, G.3, Author              
Elder, K., Author
Blayney, M., Author
Lucas-Hahn, A., Author
Niemann, H., Author
Herbert, M., Author
Schuh, M.1, Author              
Affiliations:
1Department of Meiosis, MPI for Biophysical Chemistry, Max Planck Society, ou_2205654              
2Research Group of Cytoskeletal Dynamics in Oocytes, MPI for Biophysical Chemistry, Max Planck Society, ou_2640691              
3Laboratory of Chromatin Labeling and Imaging, Max Planck Institute for Biophysical Chemistry, Max Planck Society, ou_2616691              

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Free keywords: aneuploidy; human embryo; fertilization; chromosome segregation; genome organization; centrosomes; microtubules; spindle; nuclear pore complex; dynein
 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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Language(s): eng - English
 Dates: 2021-05-072021-05-27
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.cell.2021.04.013
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 184 (11) Sequence Number: - Start / End Page: 2860 - 2877.e22 Identifier: -