eprintid: 10103462 rev_number: 14 eprint_status: archive userid: 608 dir: disk0/10/10/34/62 datestamp: 2020-07-03 10:18:38 lastmod: 2021-09-25 23:22:14 status_changed: 2020-07-03 10:18:38 type: article metadata_visibility: show creators_name: Kirkland, NJ creators_name: Yuen, AC creators_name: Tozluoglu, M creators_name: Hui, N creators_name: Paluch, EK creators_name: Mao, Y title: Tissue Mechanics Regulate Mitotic Nuclear Dynamics during Epithelial Development ispublished: inpress divisions: UCL divisions: B02 divisions: C08 divisions: D77 keywords: diaphanous, interkinetic nuclear migration, mitosis, mitotic rounding, pseudostratified epithelia, rho kinase, tissue mechanics note: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: Cell 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. date: 2020-05-14 date_type: published official_url: https://doi.org/10.1016/j.cub.2020.04.041 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1783195 doi: 10.1016/j.cub.2020.04.041 pii: S0960-9822(20)30555-8 lyricists_name: Mao, Yanlan lyricists_name: Paluch, Ewa lyricists_id: YMAOX11 lyricists_id: EPALU00 actors_name: Mao, Yanlan actors_id: YMAOX11 actors_role: owner full_text_status: public publication: Current Biology event_location: England citation: Kirkland, NJ; Yuen, AC; Tozluoglu, M; Hui, N; Paluch, EK; Mao, Y; (2020) Tissue Mechanics Regulate Mitotic Nuclear Dynamics during Epithelial Development. Current Biology 10.1016/j.cub.2020.04.041 <https://doi.org/10.1016/j.cub.2020.04.041>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10103462/1/PIIS0960982220305558.pdf