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.

中文翻译：

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Nr5a2 对于合子基因组激活是必不可少的，但对桑椹发育至关重要


早期胚胎发生由转录因子 （TF） 驱动，转录因子首先激活合子基因组，然后指定构成囊胚的谱系。尽管指定囊胚谱系的 TF 具有良好的特征，但那些发挥早期作用的 TF 仍然定义不明确。使用 TF Nr5a2 的小鼠模型，我们表明 Nr5a2 - / - 胚胎停滞在早期桑椹阶段，并表现出谱系规格改变、频繁的有丝分裂失败和大量的染色体分离缺陷。尽管 NR5A2 在合子基因组激活过程中起着次要但可测量的作用，但它主要在八细胞阶段充当主调节因子，控制参与有丝分裂、端粒维持和 DNA 修复的谱系特异性 TF 和基因的表达。我们得出结论，NR5A2 协调增殖、基因组稳定性和谱系规范，以确保正确的桑椹发育。