Mitotic spindle orientation and dynamics are fine-tuned by anisotropic tension via NuMA localisation

Abstract

Cell division orientation, which is key to cell fate and tissue morphogenesis, is influenced by mechanical forces. However, uncoupling whether divisions orient in direct response to force or indirectly via interphase cell shape remains challenging. By applying an external stretch to epithelial tissue and monitoring mitotic spindle dynamics, we show that the spindle orientation protein, NuMA, is recruited to the cell cortex earlier during mitosis in stretched tissue. This stretch-induced recruitment of NuMA coincides with the onset and subsequent amplification of dynamic spindle oscillations. We show by mathematical modelling that increased spindle oscillation indicates increased cortical force generation to orient the spindle. Additionally, we show that knockdown of NuMA reduces spindle oscillations and disrupts division orientation according to stretch and cell shape. Our results indicate that a mechanosensitive re-localisation of NuMA provides a direct response to mechanical force, fine-tuning spindle dynamics and orientation during mitosis and ensuring the accurate alignment of divisions with cell shape and anisotropic tension.