Successful navigation of the mouse preimplantation stages of development, during which three distinct blastocyst lineages are derived, represents a prerequisite for continued development. We previously identified a role for p38-mitogen-activated kinases (p38-MAPK) regulating blastocyst inner cell mass (ICM) cell fate, specifically primitive endoderm (PrE) differentiation, that is intimately linked to rRNA precursor processing, polysome formation and protein translation regulation. Here, we develop this work by assaying the role of DEAD-box RNA helicase 21 (DDX21), a known regulator of rRNA processing, in the context of p38-MAPK regulation of preimplantation mouse embryo development. We show nuclear DDX21 protein is robustly expressed from the 16-cell stage, becoming exclusively nucleolar during blastocyst maturation, a localization dependent on active p38-MAPK. siRNA-mediated clonal Ddx21 knockdown within developing embryos is associated with profound cell-autonomous and non-autonomous proliferation defects and reduced blastocyst volume, by the equivalent peri-implantation blastocyst stage. Moreover, ICM residing Ddx21 knockdown clones express the EPI marker NANOG but rarely express the PrE differentiation marker GATA4. These data contribute further significance to the emerging importance of lineage-specific translation regulation, as identified for p38-MAPK, during mouse preimplantation development.

小鼠植入前发育阶段的成功导航，在此期间衍生出三个不同的囊胚谱系，代表了持续发展的先决条件。我们之前确定了 p38-丝裂原活化激酶 (p38-MAPK) 调节胚泡内细胞团 (ICM) 细胞命运的作用，特别是原始内胚层 (PrE) 分化，这与 rRNA 前体加工、多核糖体形成和蛋白质翻译密切相关规定。在这里，我们通过分析 DEAD-box RNA 解旋酶 21 (DDX21)（一种已知的 rRNA 加工调节剂）在植入前小鼠胚胎发育的 p38-MAPK 调节中的作用来开展这项工作。我们显示核 DDX21 蛋白从 16 细胞阶段开始强烈表达，在囊胚成熟过程中完全变成核仁，依赖于活动 p38-MAPK 的本地化。siRNA介导的克隆发育中胚胎内的Ddx21敲低与严重的细胞自主和非自主增殖缺陷以及囊胚体积减少相关，相当于着床周围囊胚阶段。此外，驻留在Ddx21敲低克隆中的 ICM表达 EPI 标记 NANOG，但很少表达 PrE 分化标记 GATA4。这些数据进一步说明了谱系特异性翻译调控的重要性，如在小鼠植入前发育过程中为 p38-MAPK 所确定的那样。