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

揭示线虫中控制中心体/细胞分裂偶联/解偶联和消除的遗传调控网络

• 批准号: 217542-2012
• 负责人: Roy, Richard
• 金额: $ 2.91万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506179
• 关键词: Uncovering; genetic; regulatory; network; controlling

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.

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多种过程中发挥作用。 中心体由两个中心粒组成，它们必须在每次细胞分裂时复制，以产生在有丝分裂时将染色体分开的装置。在进化过程中，中心粒的复制和细胞分裂周期已变得密切相关，其中复制与S期事件相关，成熟（中心粒周围物质与中心粒的结合使其能够组织有丝分裂）与G2/M相关。这对于大多数细胞分裂是正确的，然而，在发育过程中，中心体周期和细胞周期的这种紧密耦合有时可以解偶联。In C.在线虫中，肠细胞在胚胎发育后期出生，但在发育后期，它们将经历四轮核内复制：基因组复制，而不分离新复制的DNA链。尽管这些S期发生在没有任何干预细胞因子的情况下，细胞不增加其中心体数量，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循环的发生有关。此外，存在于肠细胞中的中心体在内循环程序开始后不久就从上皮细胞中消除。我们已经开发出一种新的和有效的手段，揭示了各种基因的活动，参与解偶联机制，除了一种策略，以了解如何在这些情况下，中心体退役和消除。我们相信，我们的工作将提供一个有趣的新框架，以了解中心体如何使用与细胞周期相同的机制来同步其复制与基因组的复制，同时还提供了对这些神秘的细胞器如何稳定或不稳定的见解在各种发育或病理情况下。