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

极化上皮细胞的胞质分裂失败会影响顶端膜的大小和纤毛。

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Abstract

Cytokinetic abscission genes are linked to cancers and developmental disorders, but the consequences of disrupted abscission in vivo remain under-explored. 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 to investigate how stochastic abscission failures in a polarized epithelium affect the epithelial architecture. 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 biciliation. We then test whether the enlarged apical endfeet arise from filling the space of apoptotic neighbors. Remarkably, blocking apoptosis does not rescue but exacerbates the phenotypes: extra-large apical endfeet have further increased multiciliation, supernumerary centrosomes, and abnormal or multiple nuclei, although epithelial polarity is maintained. These findings elucidate the importance of proper abscission in maintaining polarized epithelial structure, and reveal that p53-mediated apoptosis is a crucial guardian of tissue architecture when cell division defects arise during development and disease.

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