Department of Veterinary and Animal Science, University of Massachusetts, Amherst, Massachusetts, United States of America.
PLoS One. 2011;6(7):e22516. doi: 10.1371/journal.pone.0022516. Epub 2011 Jul 25.
Preimplantation is a dynamic developmental period during which a combination of maternal and zygotic factors program the early embryo resulting in lineage specification and implantation. A reverse genetic RNAi screen in mouse embryos identified the WD Repeat Domain 74 gene (Wdr74) as being required for these critical first steps of mammalian development. Knockdown of Wdr74 results in embryos that develop normally until the morula stage but fail to form blastocysts or properly specify the inner cell mass and trophectoderm. In Wdr74-deficient embryos, we find activated Trp53-dependent apoptosis as well as a global reduction of RNA polymerase I, II and III transcripts. In Wdr74-deficient embryos blocking Trp53 function rescues blastocyst formation and lineage differentiation. These results indicate that Wdr74 is required for RNA transcription, processing and/or stability during preimplantation development and is an essential gene in the mouse.
着床前是一个动态的发育时期，在此期间，母体和受精卵因素的结合对早期胚胎进行编程，导致谱系特化和着床。在小鼠胚胎中的反向遗传 RNAi 筛选中，发现 WD 重复结构域 74 基因（Wdr74）对于哺乳动物发育的这些关键的第一步是必需的。Wdr74 的敲低导致胚胎在桑葚胚阶段正常发育，但不能形成囊胚或正确指定内细胞团和滋养外胚层。在 Wdr74 缺陷的胚胎中，我们发现激活了依赖 Trp53 的细胞凋亡以及 RNA 聚合酶 I、II 和 III 转录本的全面减少。在 Wdr74 缺陷的胚胎中，阻断 Trp53 功能可挽救囊胚形成和谱系分化。这些结果表明，Wdr74 在着床前发育过程中对于 RNA 转录、加工和/或稳定性是必需的，并且是小鼠中的必需基因。
