Meyer-Gerards Charlotte, Bazzi Hisham
Department of Cell Biology of the Skin, Medical Faculty, University of Cologne, Germany.
Department of Dermatology and Venereology, Medical Faculty, University of Cologne, Germany.
FEBS J. 2025 Feb;292(4):709-726. doi: 10.1111/febs.17212. Epub 2024 Jun 27.
Centrosomes are dominant microtubule organizing centers in animal cells with a pair of centrioles at their core. They template cilia during interphase and help organize the mitotic spindle for a more efficient cell division. Here, we review the roles of centrosomes in the early developing mouse and during organ formation. Mammalian cells respond to centrosome loss-of-function by activating the mitotic surveillance pathway, a timing mechanism that, when a defined mitotic duration is exceeded, leads to p53-dependent cell death in the descendants. Mouse embryos without centrioles are highly susceptible to this pathway and undergo embryonic arrest at mid-gestation. The complete loss of the centriolar core results in earlier and more severe phenotypes than that of other centrosomal proteins. Finally, different developing tissues possess varying thresholds and mount graded responses to the loss of centrioles that go beyond the germ layer of origin.
中心体是动物细胞中主要的微管组织中心,其核心是一对中心粒。它们在间期形成纤毛模板,并有助于组织有丝分裂纺锤体以实现更高效的细胞分裂。在这里,我们综述了中心体在小鼠早期发育和器官形成过程中的作用。哺乳动物细胞通过激活有丝分裂监测途径来应对中心体功能丧失,这是一种定时机制,当超过规定的有丝分裂持续时间时,会导致后代细胞中p53依赖性细胞死亡。没有中心粒的小鼠胚胎对该途径高度敏感,并在妊娠中期发生胚胎停滞。中心粒核心的完全丧失比其他中心体蛋白导致更早、更严重的表型。最后,不同的发育组织对中心粒丧失具有不同的阈值,并对其产生分级反应,这种反应超出了起源的胚层。