Mitotic spindle orientation in epithelial homeostasis and plasticity

Polarized epithelia are a foundation of organ and appendage structures throughout Metazoa and serve as a physical barrier to preserve physiological functions. In proliferating epithelia, planar cell division occurs by orienting the mitotic spindle within the plane of the epithelium to ensure tissue organization. Conversely, loss of tissue architecture is a hallmark of carcinoma, and aberrant spindle orientation is hypothesized to contribute to tissue disorganization through dysplasia and cell dissemination. Recent in vivo studies have uncovered a role of planar spindle alignment in the robust maintenance of tissue architecture, which accompanies homeostatic mechanisms such as cell delamination and re-integration of misplaced cells following abnormal cell division. Furthermore, perpendicular spindle orientation shifts have been suggested as causes of cell fate change and epithelial plasticity manifested by epithelial-to-mesenchymal transition. This review describes the mechanism by which planar spindle orientation is tightly regulated and discusses the roles of mitotic spindle orientation in epithelial development and disease.