<i>Nr5a2</i> is dispensable for zygotic genome activation but essential for morula development

Early embryogenesis is driven by transcription factors (TFs) that first activate the zygotic genome and then specify the lineages constituting the blastocyst. Although the TFs specifying the blastocyst's lineages are well characterized, those playing earlier roles remain poorly defined. Using mouse models of the TF <i>Nr5a2</i>, we show that <i>Nr5a2</i><sup>-/-</sup> embryos arrest at the early morula stage and exhibit altered lineage specification, frequent mitotic failure, and substantial chromosome segregation defects. Although NR5A2 plays a minor but measurable role during zygotic genome activation, it predominantly acts as a master regulator at the eight-cell stage, controlling expression of lineage-specifying TFs and genes involved in mitosis, telomere maintenance, and DNA repair. We conclude that NR5A2 coordinates proliferation, genome stability, and lineage specification to ensure correct morula development.

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Publication Details

Journal
Science
Published
2024-10-03
DOI
https://doi.org/10.1126/science.adg7325
Citations
18
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
4.21

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article

Nr5a2 is dispensable for zygotic genome activation but essential for morula development

Sandrine Vandormael‐Pournin, Nicola Festuccia, Rémi-Xavier Coux, Michel Cohen‐Tannoudji et al.
18 citations
Science
CRISPR and Genetic Engineering
4.21
article

Nr5a2 is dispensable for zygotic genome activation but essential for morula development

Sandrine Vandormael‐Pournin, Nicola Festuccia, Rémi-Xavier Coux, Michel Cohen‐Tannoudji, Anna Geiselman, Francina Langa‐Vives, Pablo Navarro, Almira Chervova, Inma González, Guillaume Giraud Collet
article en
18 citations

Abstract

Early embryogenesis is driven by transcription factors (TFs) that first activate the zygotic genome and then specify the lineages constituting the blastocyst. Although the TFs specifying the blastocyst's lineages are well characterized, those playing earlier roles remain poorly defined. Using mouse models of the TF <i>Nr5a2</i>, we show that <i>Nr5a2</i><sup>-/-</sup> embryos arrest at the early morula stage and exhibit altered lineage specification, frequent mitotic failure, and substantial chromosome segregation defects. Although NR5A2 plays a minor but measurable role during zygotic genome activation, it predominantly acts as a master regulator at the eight-cell stage, controlling expression of lineage-specifying TFs and genes involved in mitosis, telomere maintenance, and DNA repair. We conclude that NR5A2 coordinates proliferation, genome stability, and lineage specification to ensure correct morula development.

ScienceVol. 386(6717)
Centre National de la Recherche Scientifique (FR), Institut Pasteur (FR), Université Paris Cité (FR), Sorbonne Université (FR), Sorbonne Paris Cité (FR), Epigénétique et Destin Cellulaire (FR), Université Paris 1 Panthéon-Sorbonne (FR)
Agence Nationale de la Recherche, Centre National de la Recherche Scientifique
Openalex Percentile: Top 5%
CRISPR and Genetic Engineering
4.21
DOIOpen Access PDFOpenAlex
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