Cytokinetic abscission failures in a polarized epithelium affect apical membrane size and cilia

Cytokinetic abscission is the last step of cell division, during which the intercellular bridge between daughter cells is severed. While abscission genes are linked to cancers and developmental disorders, the consequences of disrupted abscission in vivo have remained under-explored. For a polarized epithelium to expand or renew, cells within it must divide while maintaining polarity, cell junctions, and epithelial integrity. They undergo a polarized form of cytokinesis in which abscission occurs at the apical membrane. Here, we investigate how stochastic abscission failures in a polarized epithelium disrupt epithelial architecture, using mouse neuroepithelium as a model. Previously we showed that in the forebrain of Cep55 knockout (KO) mouse embryos, a subset of neuroepithelial stem cells (NSCs) fail abscission and become binucleate, and some of those undergo p53-mediated apoptosis. Here we use the Cep55 KO forebrain to focus on how disrupting abscission in a polarized epithelium affects the apical membrane structure. We find that NSCs in Cep55 KO neuroepithelium have preserved epithelial polarity and integrity. However, they have enlarged apical membranes (called apical endfeet), longer primary cilia, and increased bi-ciliation. We test whether the enlarged apical endfeet arise from filling the space of apoptotic neighbors. However, blocking apoptosis does not rescue but exacerbates the phenotypes: extra-large apical endfeet have further increased multi-ciliation, supernumerary centrosomes, and abnormal or multiple nuclei. These findings show the importance of proper abscission in a polarized epithelium to maintain epithelial structure, and the need for p53-mediated apoptosis to protect the tissue in the face of stochastic abscission failures.