Expression of the novel maternal centrosome assembly factor Wdr8 is required for vertebrate embryonic mitoses
Expression of the novel maternal centrosome assembly factor Wdr8 is required for vertebrate embryonic mitoses
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DOI：
10.1038/ncomms14090
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发表时间：
2017-01-18
影响因子：
16.6
通讯作者：
Gruss, Oliver J.
中科院分区：
文献类型：
--
作者：
Inoue, Daigo;Stemmer, Manuel;Gruss, Oliver J.
第一个中心体的组装发生在受精后，当雄性中心粒从卵细胞质中募集中心粒周围物质（PCM）时。在早期胚胎发生过程中中心体的正确组装的机制仍然不清楚。我们确定Wdr 8作为一种新的母系必需蛋白，是所需的中心体组装在胚胎有丝分裂的青鳉（Oryzias latipes）。通过CRISPR-Cas9介导的敲除，母体/合子Wdr 8-null（m/zWdr 8（-/-））卵裂球表现出中心体结构的严重缺陷，导致不对称分裂、多极有丝分裂纺锤体和染色体比对错误。通过其WD 40结构域，Wdr 8与中心粒卫星蛋白SSX 2 IP相互作用。结合靶向基因敲除和母体必需的Wdr 8-SSX 2 IP复合物的体内重建揭示了母体中心体蛋白与合子基因组稳定性之间的重要联系，用于精确的脊椎动物胚胎发生。我们的方法提供了一种区分早期胚胎中母亲和父亲影响的方法，并有助于理解人类不育症的分子缺陷。
The assembly of the first centrosome occurs upon fertilisation when male centrioles recruit pericentriolar material (PCM) from the egg cytoplasm. The mechanisms underlying the proper assembly of centrosomes during early embryogenesis remain obscure. We identify Wdr8 as a novel maternally essential protein that is required for centrosome assembly during embryonic mitoses of medaka (Oryzias latipes). By CRISPR-Cas9-mediated knockout, maternal/zygotic Wdr8-null (m/zWdr8(-/-)) blastomeres exhibit severe defects in centrosome structure that lead to asymmetric division, multipolar mitotic spindles and chromosome alignment errors. Via its WD40 domains, Wdr8 interacts with the centriolar satellite protein SSX2IP. Combining targeted gene knockout and in vivo reconstitution of the maternally essential Wdr8-SSX2IP complex reveals an essential link between maternal centrosome proteins and the stability of the zygotic genome for accurate vertebrate embryogenesis. Our approach provides a way of distinguishing maternal from paternal effects in early embryos and should contribute to understanding molecular defects in human infertility.