Dual-spindle formation in zygotes keeps parental genomes apart in early mammalian embryos

Reichmann, Judith; Nijmeijer, Bianca; Hossain, M. Julius; Eguren, Manuel; Schneider, Isabell; Politi, Antonio Z.; Roberti, M. Julia; Hufnagel, Lars; Hiiragi, Takashi; Ellenberg, Jan

doi:10.1126/science.aar7462

Cited by 128 publications

(114 citation statements)

References 33 publications

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“…These observations aligned with previous indications that the maternal and paternal genomes are spatially segregated in zygotes (54,55) and remain so to a lesser extent as late as the 8-cell stage ( (25,26); fig. S8).…”

supporting

confidence: 91%

The genome-wide, multi-layered architecture of chromosome pairing in earlyDrosophilaembryos

Erceg

Abed

Goloborodko

et al. 2018

Preprint

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Genome organization involves cis and trans chromosomal interactions, both implicated in gene regulation, development, and disease. Here, we focused on trans interactions in Drosophila, where homologous chromosomes are paired in somatic cells from embryogenesis through adulthood. We first addressed the long-standing question of whether pairing extends genome-wide and, to this end, developed a haplotype-resolved Hi-C approach that uses a new strategy to minimize homolog misassignment and thus robustly distinguish trans-homolog from cis contacts. This approach revealed striking genome-wide pairing in Drosophila embryos. Moreover, we discovered pairing to be surprisingly structured, with trans-homolog domains and interaction peaks, many coinciding with the positions of analogous cis features. We also found a significant correlation between pairing and the chromatin accessibility mediated by the pioneer factor Zelda. Our findings reveal a complex, highly structured organization underlying homolog pairing, first discovered more than a century ago.

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supporting

confidence: 91%

The genome-wide, multi-layered architecture of chromosome pairing in earlyDrosophilaembryos

Erceg

Abed

Goloborodko

et al. 2018

Preprint

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“…It was recently shown that in mice, the first zygotic mitosis occurs on two separate, and often parallel, spindles (Reichmann et al, 2018). If the mechanism of pronuclear membrane remodeling in C. elegans applies to vertebrates, then these two spindles may be separated by remnants of the pronuclear membranes.…”

Section: Resultsmentioning

confidence: 99%

C. elegans pronuclei fuse after fertilization through a novel membrane structure

Rahman

Chang

Harned

et al. 2019

Journal of Cell Biology

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After fertilization, parental genomes are enclosed in two separate pronuclei. In Caenorhabditis elegans, and possibly other organisms, when the two pronuclei first meet, the parental genomes are separated by four pronuclear membranes. To understand how these membranes are breached to allow merging of parental genomes we used focused ion beam scanning electron microscopy (FIB-SEM) to study the architecture of the pronuclear membranes at nanometer-scale resolution. We find that at metaphase, the interface between the two pronuclei is composed of two membranes perforated by fenestrations ranging from tens of nanometers to several microns in diameter. The parental chromosomes come in contact through one of the large fenestrations. Surrounding this fenestrated, two-membrane region is a novel membrane structure, a three-way sheet junction, where the four membranes of the two pronuclei fuse and become two. In the plk-1 mutant, where parental genomes fail to merge, these junctions are absent, suggesting that three-way sheet junctions are needed for formation of a diploid genome.

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“…The number of direct unequal cleavage divisions at the zygote stage seems to be insufficient to account for all the observed haploid and uniparental cells at the eight-cell-stage embryos derived from fertilizations with damaged sperm. Because parental genomes still occupy distinct territories at the two-cell stage (37,38), uniparental and haploid cells may also be formed by unequal cleavages at this stage of development. The observation that frequently only half of the cells of eight-cell-stage embryos were haploid/uniparental may indicate heterogoneic cell divisions of two-cell-stage blastomeres.…”

Section: Discussionmentioning

confidence: 99%

Sperm DNA damage causes genomic instability in early embryonic development

et al. 2020

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Genomic instability is common in human embryos, but the underlying causes are largely unknown. Here, we examined the consequences of sperm DNA damage on the embryonic genome by single-cell whole-genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by γ-radiation. Sperm DNA damage primarily leads to fragmentation of the paternal chromosomes followed by random distribution of the chromosomal fragments over the two sister cells in the first cell division. An unexpected secondary effect of sperm DNA damage is the induction of direct unequal cleavages, which include the poorly understood heterogoneic cell divisions. As a result, chaotic mosaicism is common in embryos derived from fertilizations with damaged sperm. The mosaic aneuploidies, uniparental disomies, and de novo structural variation induced by sperm DNA damage may compromise fertility and lead to rare congenital disorders when embryos escape developmental arrest.

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Dual-spindle formation in zygotes keeps parental genomes apart in early mammalian embryos

Cited by 128 publications

References 33 publications

The genome-wide, multi-layered architecture of chromosome pairing in earlyDrosophilaembryos

The genome-wide, multi-layered architecture of chromosome pairing in earlyDrosophilaembryos

C. elegans pronuclei fuse after fertilization through a novel membrane structure

Sperm DNA damage causes genomic instability in early embryonic development

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