Spindle Assembly Checkpoint Genes Reveal Distinct as well as Overlapping Expression that Implicates MDF-2/Mad2 in Postembryonic Seam Cell Proliferation in Caenorhabditis elegans

Background: The spindle assembly checkpoint (SAC) delays anaphase onset by inhibiting the activity of theanaphase promoting complex/cyclosome (APC/C) until all of the kinetochores have properly attached to thespindle. The importance of SAC genes for genome stability is well established; however, the roles these genes play,during postembryonic development of a multicellular organism, remain largely unexplored.Results: We have used GFP fusions of 5’ upstream intergenic regulatory sequences to assay spatiotemporalexpression patterns of eight conserved genes implicated in the spindle assembly checkpoint function inCaenorhabditis elegans. We have shown that regulatory sequences for all of the SAC genes drive ubiquitous GFPexpression during early embryonic development. However, postembryonic spatial analysis revealed distinct, tissuespecificexpression of SAC genes with striking co-expression in seam cells, as well as in the gut. Additionally, weshow that the absence of MDF-2/Mad2 (one of the checkpoint genes) leads to aberrant number and alignment ofseam cell nuclei, defects mainly attributed to abnormal postembryonic cell proliferation. Furthermore, we showthat these defects are completely rescued by fzy-1(h1983)/CDC20, suggesting that regulation of the APC/CCDC20 bythe SAC component MDF-2 is important for proper postembryonic cell proliferation.Conclusion: Our results indicate that SAC genes display different tissue-specific expression patterns duringpostembryonic development in C. elegans with significant co-expression in hypodermal seam cells and gut cells,suggesting that these genes have distinct as well as overlapping roles in postembryonic development that may ormay not be related to their established roles in mitosis. Furthermore, we provide evidence, by monitoring seamcell lineage, that one of the checkpoint genes is required for proper postembryonic cell proliferation. Importantly,our research provides the first evidence that postembryonic cell division is more sensitive to SAC loss, in particularMDF-2 loss, than embryonic cell division