aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda in Drosophila neuroblasts

Abstract

Cell fate generation can rely on the unequal distribution of molecules during progenitor cell division in the nervous system of vertebrates and invertebrates. Here we address asymmetric fate determinant localization in the developing Drosophila nervous system, focussing on the control of asymmetric Miranda distribution in larval neuroblasts. We used live imaging of neuroblast polarity reporters at endogenous levels of expression to address Miranda localization during the cell cycle. We reveal that the regulation and dynamics of cortical association of Miranda in interphase and mitosis are different. In interphase Miranda binds directly to the plasma membrane. At the onset of mitosis, Miranda is phosphorylated by aPKC and displaced from the PM. After nuclear envelope breakdown asymmetric localization of Miranda requires actomyosin activity. Therefore, Miranda phosphorylation by aPKC and differential binding to the actomyosin network are required at distinct phases of the cell cycle to polarize fate determinant localization.