Moesin is a major regulator of centrosome behavior in epithelial cells with extra centrosomes

Abstract

Centrosome amplification has severe consequences during development and is thought to contribute to a variety of diseases such as cancer and microcephaly. However, the adverse effects of centrosome amplification in epithelia are still not known. Here, we investigate the consequences of centrosome amplification in the Drosophila wing disc epithelium. We found that epithelial cells exhibit mechanisms of clustering but also inactivation of extra centrosomes. Importantly, these mechanisms are not fully efficient, and both aneuploidy and cell death can be detected. Epithelial cells with extra centrosomes generate tumors when transplanted into WT hosts and inhibition of cell death results in tissue over-growth and disorganization. Using SILAC-fly, we found that Moesin, a FERM domain protein, is specifically upregulated in wing discs with extra centrosomes. Moesin localizes to the centrosomes and mitotic spindle during mitosis, and we show that Moesin upregulation influences extra-centrosome behavior and robust bipolar spindle formation. This study provides a mechanistic explanation for the increased aneuploidy and transformation potential primed by centrosome amplification in epithelial tissues.