PDF(Pubmed)
Abstract：
Embryo size, specification, and homeostasis are regulated by a complex gene regulatory and signaling network. Here we used gene expression signatures of Wnt-activated mouse embryonic stem cell (mESC) clones to reverse engineer an mESC regulatory network. We identify NKX1-2 as a novel master regulator of preimplantation embryo development. We find that Nkx1-2 inhibition reduces nascent RNA synthesis, downregulates genes controlling ribosome biogenesis, RNA translation, and transport, and induces severe alteration of nucleolus structure, resulting in the exclusion of RNA polymerase I from nucleoli. In turn, NKX1-2 loss of function leads to chromosome missegregation in the 2- to 4-cell embryo stages, severe decrease in blastomere numbers, alterations of tight junctions (TJs), and impairment of microlumen coarsening. Overall, these changes impair the blastocoel expansion-collapse cycle and embryo cavitation, leading to altered lineage specification and developmental arrest.
摘要：
胚胎大小,规格,和稳态受复杂的基因调控和信号网络的调节。在这里，我们使用Wnt激活的小鼠胚胎干细胞（mESC）克隆的基因表达特征来反向工程mESC调控网络。我们将NKX1-2鉴定为植入前胚胎发育的新型主调节因子。我们发现Nkx1-2抑制减少新生RNA合成，下调控制核糖体生物发生的基因，RNA翻译,和运输,并引起核仁结构的严重改变，导致RNA聚合酶I从核仁中排除。反过来,NKX1-2功能丧失导致2至4细胞胚胎阶段的染色体不分离，卵裂球数量严重减少，紧密连接（TJ）的改变，和微内腔粗化的损害。总的来说,这些变化损害了胚层扩张-塌陷周期和胚胎空化，导致谱系规范和发育停滞的改变。
