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

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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.