Abstract
Proper assembly of the spindle apparatus is crucially important for faithful chromosome segregation during anaphase. Thanks to the effort over the last decades, we have very detailed information about many events leading to spindle assembly and chromosome segregation, however we still do not understand certain aspects, including, for example, spindle length control. When tight regulation of spindle size is lost, chromosome segregation errors emerge. Currently, there are several hypotheses trying to explain the molecular mechanism of spindle length control. The number of kinetochores, activity of molecular rulers, intracellular gradients, cell size, limiting spindle components, and the balance of the spindle forces seem to contribute to spindle size regulation, however some of these mechanisms are likely specific to a particular cell type. In search for a general regulatory mechanism, in our study we focused on the role of cell size and nuclear to cytoplasmic ratio in this process. To this end, we used relatively large cells isolated from 2-cell mouse embryos. Our results showed that the spindle size upper limit is not reached in these cells and suggest that accurate control of spindle length requires balanced ratio between nuclear and cytoplasmic volumes.
Highlights
Faithful chromosome segregation is vital for transfer of intact genetic information into the daughter cells
In order to study the relationship between cell volume and spindle length, we employed a challenging procedure, during which two or three blastomeres from 2-cell embryos were electrofused, giving rise to cells with double or triple volume compared to an intact blastomere
We focused on general rules regulating spindle size, namely the role of cell size, nuclear to cytoplasmic ratio, and number of chromosomes in this process
Summary
Faithful chromosome segregation is vital for transfer of intact genetic information into the daughter cells. From engagement of the chromosomes into division by capturing kinetochores during the early stages of mitosis, through their alignment at the metaphase plate, up to the distribution of sister chromatids into daughter cells during the final stages of mitosis, all these functions are mechanistically carried out by the spindle. A clear example is the regulation of spindle length, which is important for faithful chromosome segregation [3], as well as for asymmetric cell division [4]. It PLOS ONE | DOI:10.1371/journal.pone.0149535 February 17, 2016
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