Centrosomes, composed of two centrioles and pericentriolar material, organize mitotic spindles during cell division and template cilia during interphase. The first few divisions during mouse development occur without centrioles, which form around embryonic day (E) 3. However, disruption of centriole biogenesis in Sas‐4 null mice leads to embryonic arrest around E9. Centriole loss in Sas‐4^−/− embryos causes prolonged mitosis and p53‐dependent cell death. Studies in vitro discovered a similar USP28‐, 53BP1‐, and p53‐dependent mitotic surveillance pathway that leads to cell cycle arrest. In this study, we show that an analogous pathway is conserved in vivo where 53BP1 and USP28 are upstream of p53 in Sas‐4^−/− embryos. The data indicate that the pathway is established around E7 of development, four days after the centrioles appear. Our data suggest that the newly formed centrioles gradually mature to participate in mitosis and cilia formation around the beginning of gastrulation, coinciding with the activation of mitotic surveillance pathway upon centriole loss.

中文翻译：

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逐渐的中心粒成熟与小鼠发育中的有丝分裂监测途径有关

中心体由两个中心体和中心体周围的物质组成，在细胞分裂过程中组织有丝分裂纺锤体，在相间期组织模板纤毛。小鼠发育过程中的前几个分裂在没有中心粒的情况下发生，在胚胎第3天左右形成。但是，Sas-4缺失小鼠中的中心粒生物发生破坏会导致E9附近的胚胎停滞。Sas-4 ^-/-胚胎中的离心损失会导致有丝分裂时间延长和p53依赖性细胞死亡。研究体外发现了一个类似的USP28-，53BP1-和p53依赖的有丝分裂监督途径，导致细胞周期停滞。在这项研究中，我们表明在体内保守的类似途径，其中53BP1和USP28在Sas-4中位于p53的上游^-/-胚胎。数据表明，在中心粒出现后四天，该途径在发育的E7周围建立。我们的数据表明，新形成的中心粒逐渐成熟，以在胃芽形成开始时参与有丝分裂和纤毛形成，这与中心粒丢失后有丝分裂监测途径的激活相吻合。