Formation of the hatching mouse blastocyst marks the end of preimplantation development, whereby previous cell cleavages culminate in the formation of three distinct cell lineages (trophectoderm, primitive endoderm and epiblast). We report that dysregulated expression of Wwc2, a genetic paralog of Kibra/Wwc1 (a known activator of Hippo-signaling, a key pathway during preimplantation development), is specifically associated with cell autonomous deficits in embryo cell number and cell division abnormalities. Division phenotypes are also observed during mouse oocyte meiotic maturation, as Wwc2 dysregulation blocks progression to the stage of meiosis II metaphase (MII) arrest and is associated with spindle defects and failed Aurora-A kinase (AURKA) activation. Oocyte and embryo cell division defects, each occurring in the absence of centrosomes, are fully reversible by expression of recombinant HA-epitope tagged WWC2, restoring activated oocyte AURKA levels. Additionally, clonal embryonic dysregulation implicates Wwc2 in maintaining the pluripotent epiblast lineage. Thus, Wwc2 is a novel regulator of meiotic and early mitotic cell divisions, and mouse blastocyst cell fate.

孵化小鼠胚泡的形成标志着植入前发育的结束，从而先前的细胞分裂最终形成了三个不同的细胞谱系（滋养外胚层，原始内胚层和上皮细胞）。我们报告说，表达异常第二次世界大战，是 基布拉/ WWC1（已知的河马信号激活剂，即着床前发育的关键途径），与胚胎细胞数量和细胞分裂异常中的细胞自主性缺陷特别相关。在小鼠卵母细胞减数分裂成熟过程中也观察到分区表型，因为第二次世界大战失调阻止进展到减数分裂II中期（MII）停滞阶段，并与纺锤体缺陷和Aurora-A激酶（AURKA）激活失败有关。卵母细胞和胚胎细胞分裂缺陷均在不存在中心体的情况下发生，可通过表达重组HA表位标记的WWC2来完全逆转，从而恢复活化的卵母细胞AURKA水平。此外，克隆胚胎失调也意味着第二次世界大战维持多能成骨细胞谱系。从而，第二次世界大战 是减数分裂和早期有丝分裂细胞分裂以及小鼠胚泡细胞命运的新型调节剂。