DSSS - Switching cycles: Function and regulation of non-canonical cell cycles during development

A fundamental property of life is the ability of cells to undergo cell cycles, in which they duplicate their genetic material and divide into two daughter cells. While the basic principles of the cell cycle have been intensively studied in yeast and mammalian cells in culture, much less is known about cell-cycle regulation during multicellular development. In many animal tissues, cells undergo endomitosis, a non-canonical cell cycle in which cells undergo all phases of the canonical cell cycle except cytokinesis, leading to a 4N or binucleate cell. Although endomitosis cycles are widespread among multicellular species, it is unclear how cells transition to endomitosis, and what the function is of binucleation for cells and tissues. In our lab, we make use of the C. elegans intestinal lineage as a model to study endomitosis regulation and function. Using live-imaging, single-molecule FISH and RNA-sequencing we found that intestinal cells switch from canonical to endomitosis cycles during late embryogenesis by repressing essential cytokinesis regulators. Furthermore, we generated tools to specifically inhibit intestinal endomitosis and identified an important function of binucleation in fine-tuning tissue-specific gene expression during development. Together, our work is shedding light into the regulation and function of non-canonical cycles during multicellular development.