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

• 成果类型: Article
• 署名作者: Festuccia, Nicola; Vandormael-Pournin, Sandrine; Chervova, Almira; Geiselman, Anna; Langa-Vives, Francina; Coux, Remi-Xavier; Gonzalez, Inma; Collet, Guillaume Giraud; Cohen-Tannoudji, Michel; Navarro, Pablo
• 署名单位: Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Sorbonne Universite; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Universite Paris Cite
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9156
• DOI: 10.1126/science.adg7325
• 发表日期: 2024-10-04
• 关键词: early mouse development; gene-expression; r/bioconductor package; nanog; chromatin; reveals; oocytes; roles; esrrb; specification

摘要

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.