Cell–cell adhesion accounts for the different orientation of columnar and hepatocytic cell divisions

Mitotic spindle alignment with the basal or substrate-contacting domain ensures that dividing epithelial cells remain in the plane of the monolayer. Spindle orientation with respect to the substratum is established in metaphase coincident with maximal cell rounding, which enables unobstructed spindle rotation. Misaligned metaphase spindles are believed to result in divisions in which one daughter loses contact with the basal lamina. Here we describe a rescue mechanism that drives substrate-parallel spindle alignment of quasi-diagonal metaphase spindles in anaphase. It requires a Rho-and E-cadherin adhesion-dependent, substrate-parallel contractile actin belt at the apex that governs anaphase cell flattening. In contrast to monolayered Madin-Darby canine kidney cells, hepatocytic epithelial cells, which typically feature tilted metaphase spindles, lack this anaphase flattening mechanism and as a consequence maintain their spindle tilt through cytokinesis. This results in out-of-monolayer divisions, which we propose contribute to the stratified organization of hepatocyte cords in vivo.