Abstract
SummaryCell divisions are essential for tissue growth. In pseudostratified epithelia, where nuclei are staggered across the tissue, each nucleus migrates apically before undergoing mitosis. Successful apical nuclear migration is critical for planar-orientated cell divisions in densely packed epithelia. Most previous investigations have focused on the local cellular mechanisms controlling nuclear migration. Inter-species and inter-organ comparisons of different pseudostratified epithelia suggest global tissue architecture may influence nuclear dynamics, but the underlying mechanisms remain elusive. Here, we use the developing Drosophila wing disc to systematically investigate, in a single epithelial type, how changes in tissue architecture during growth influence mitotic nuclear migration. We observe distinct nuclear dynamics at discrete developmental stages, as epithelial morphology changes. We use genetic and physical perturbations to show a direct effect of cell density on mitotic nuclear positioning. We find Rho kinase and Diaphanous, which facilitate mitotic cell rounding in confined cell conditions, are essential for efficient apical nuclear movement. Perturbation of Diaphanous causes increasing defects in apical nuclear migration as the tissue grows and cell density increases, and these defects can be reversed by acute physical reduction of cell density. Our findings reveal how the mechanical environment imposed on cells within a tissue alters the molecular and cellular mechanisms adopted by single cells for mitosis.
Highlights
Successful mitosis in densely packed epithelia relies on the ability of cells to round up
Wing Disc Development Is Associated with Increased Tissue Height, Nuclear Layering, and Cell Density To identify features of cell and tissue morphology that may influence mitotic nuclear behavior, we first characterized how the apico-basal architecture of the wing disc changes during development
When normalized to account for the potential distance they must translocate to the apical surface at each stage, we found that mitotic nuclei were most apically distributed at 96 h after egg laying (AEL) compared to wing discs at 72 and 120 h AEL (Figures S1G and S1H)
Summary
Successful mitosis in densely packed epithelia relies on the ability of cells to round up. Mitotic rounding is required to resist the mechanical constraints exerted by neighboring cells, and when defective can lead to aneuploidy and division failure [3, 8]. Mitotic cells round up at the apical surface of the tissue, facilitating planar-orientated cell divisions [9, 10]. Pseudostratified epithelia (PSE), where nuclei are staggered across an epithelial monolayer, are among the most densely packed tissue structures. Nuclei must translocate to the apical surface prior to mitosis, a process referred to as interkinetic nuclear migration (IKNM) [14]
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