Uncovering the genetic regulatory network controlling centrosome/cell division coupling/uncoupling and elimination in C. elegans

中心体是主要的细胞微管组织中心，因此它在细胞分裂、轴突伸长和纤毛发生等不同过程中发挥作用。中心体由两个中心粒组成，两个中心粒必须随着每个细胞分裂而复制，以产生在有丝分裂时分离染色体的装置。在进化过程中，中心粒的复制和细胞分裂周期变得密切相关，从而复制与S期事件有关，成熟(中心粒周围物质与中心粒结合，使其能够组织有丝分裂)与G2/M有关。这是对大多数细胞分裂的情况。然而，在发育过程中，中心体周期和细胞周期的这种密切耦合有时可以分离。在线虫中，肠道细胞是在胚胎发育后期出生的，但在发育后期，它们将经历四轮内复制：复制基因组，而不分离新复制的DNA链。尽管在没有任何细胞分裂素的情况下出现了这些S期，但细胞并没有增加其中心体数量，这表明中心粒在某种程度上与细胞周期解偶联，这种解偶联似乎与内周期的开始有关。此外，肠细胞中存在的中心体在内周期程序开始后不久就从上皮细胞中消除。除了了解中心体在这些情况下是如何退役和消除的策略外，我们还开发了一种新颖而有效的方法来揭示参与解偶联机制的各种基因活动。我们相信，我们的工作将为理解中心体如何使用与细胞周期相同的机制来使其与基因组的复制同步提供一个有趣的新框架，同时也为这些神秘的细胞器在各种发育或病理情况下如何稳定或去稳定提供了洞察。

The centrosome is the major cellular microtubule organizing centre and as such it functions in such diverse processes as cell division, axon elongation, and ciliogenesis. The centrosome is made up of two centrioles that must duplicate with each cell division to give rise to the apparatus that will separate the chromosomes at mitosis. Over the course of evolution, the duplication of the centrioles and the cell division cycle have become intimately linked, whereby duplication is associated with S phase events and maturation (association of pericentriolar material with the centrioles to render them capable of organising mitosis) is linked to G2/M. This is true for most cell divisions however, during development, this intimate coupling of the centrosome cycle and the cell cycle can sometimes be uncoupled. In C. elegans, the intestinal cells are born during late embryogenesis, but later during development they will undergo four rounds of endoreduplication: duplication of the genome without separating the newly duplicated DNA strands. Despite these S phases that occur in the absence of any intervening cytokineses, the cells do not increase their centrosome numbers indicating that the centrioles are somehow uncoupled from the cell cycle and this uncoupling seems to be associated with the onset of the endocycles. Moreover, the centrosomes that are present in the intestinal cells are eliminated from the epithelium shortly after the onset of the endocycle program. We have developed a novel and efficient means of unveiling the various gene activities that are involved in the uncoupling mechanism in addition to a strategy to understand how centrosomes are decommissioned and eliminated during these circumstances. We believe that our work will provide an interesting new framework in understanding how the centrosome uses the same machinery as the cell cycle to synchronise its duplication with that of the genome, while also providing insight into how such mysterious organelles may be stabilized or de-stabilized in various developmental or pathological situations.