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

Autor: Festuccia N; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France., Vandormael-Pournin S; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France., Chervova A; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France., Geiselmann A; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France.; Sorbonne Université, Complexité du Vivant, 75005 Paris, France., Langa-Vives F; Mouse Genetics Engineering Center, C2RA, Institut Pasteur, 75015 Paris, France., Coux RX; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France., Gonzalez I; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France., Collet GG; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France.; Université Paris Cité, BioSPC, 75013 Paris, France., Cohen-Tannoudji M; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France., Navarro P; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Oct 04; Vol. 386 (6717), pp. eadg7325. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1126/science.adg7325
Abstrakt: 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 Nr5a2 , we show that Nr5a2 -/- 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.
Databáze: MEDLINE
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