Aguilar‐Aragon, MarioBonello, TeresaBell, Graham P.Fletcher, GeorginaThompson, Barry2020-09-232020-09-231469-221Xhttp://hdl.handle.net/1885/211368Epithelial cells undergo cortical rounding at the onset of mitosis to enable spindle orientation in the plane of the epithelium. In cuboidal epithelia in culture, the adherens junction protein Ecadherin recruits Pins/LGN/GPSM2 and Mud/NuMA to orient the mitotic spindle. In the pseudostratified columnar epithelial cells of Drosophila, septate junctions recruit Mud/NuMA to orient the spindle, while Pins/LGN/GPSM2 is surprisingly dispensable. We show that these pseudostratified epithelial cells downregulate Ecadherin as they round up for mitosis. Preventing cortical rounding by inhibiting Rho-kinase-mediated actomyosin contractility blocks downregulation of E-cadherin during mitosis. Mitotic activation of Rho-kinase depends on the RhoGEF ECT2/Pebble and its binding partners RacGAP1/MgcRacGAP/CYK4/Tum and MKLP1/KIF23/ZEN4/ Pav. Cell cycle control of these Rho activators is mediated by the Aurora A and B kinases, which act redundantly during mitotic rounding. Thus, in Drosophila pseudostratified epithelia, disruption of adherens junctions during mitosis necessitates planar spindle orientation by septate junctions to maintain epithelial integrity.This work was funded by the Francis Crick Institute (FC0010180), which is a joint initiative of Cancer Research UK (FC0010180), the Medical Research Council (FC001180), and Wellcome (FC001180). This work was also funded by The Australian National Universityapplication/pdfen-AU© 2020 The Authorshttp://creativecommons.org/licenses/by/4.0/202010.15252/embr.2019497002020-06-23CC BY 4.0 license