The actin cytoskeleton governs apical mitosis and daughter cell dispersion in intestinal epithelia

Abstract

Cell proliferation is critical for maintaining the absorptive, protective and regenerative functions of the small intestine throughout adulthood. Interphase nuclei are positioned near the basal surface of the intestinal epithelium, but during mitosis, chromosomes are located apically. The molecular basis for apical-basal DNA positioning and its consequences for tissue homeostasis are poorly understood. Here, we image and pharmacologically perturb these behaviors in live murine intestinal organoids. We find that apical and basal DNA movements occur as a result of mitosis-coupled actin rearrangements that alter the basolateral shape of dividing cells, while the apical cell surface remains confined by cell-cell contacts that persist throughout mitosis. Strikingly, these polarized shape changes allow neighboring cells to insert between nascent daughters, intermingling cells of different lineages. In summary, polarized rearrangements of the actin cytoskeleton govern the mitotic behavior of intestinal epithelial cells and lead to interspersion of cell lineages.