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

• Published in: eLife Vol. 7; no. 3; pp. 773 - 788
• Main Authors: Hannaford, Matthew Robert, Ramat, Anne, Loyer, Nicolas, Januschke, Jens
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 24.01.2018; eLife Sciences Publications Ltd; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: Actomyosin; Actomyosin - metabolism; Adapter proteins; Animals; asymmetric cell division; Brain; Cell cycle; Cell Cycle Proteins - metabolism; Cell division; Cell fate; Cell membranes; Cytoplasm; Developmental Biology; Drosophila; Drosophila - growth & development; Drosophila Proteins - metabolism; Experiments; Fate; Immunoglobulins; Insects; Interphase; Kinases; Larva - growth & development; Life Sciences; Localization; Mitosis; Nervous system; Neuroblasts; Neurons - physiology; Phosphorylation; polarity; Progenitor cells; Protein Binding; Protein Kinase C - metabolism; Protein Processing, Post-Translational; Regulation; Retention; Stem Cells - physiology; Canada; Venezuela; asymmetric cell division; stem cells; Drosophila; developmental biology; D. melanogaster; neuroblasts; polarity
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.29939

Cell fate assignment in the nervous system of vertebrates and invertebrates often hinges on the unequal distribution of molecules during progenitor cell division. We address asymmetric fate determinant localization in the developing nervous system, specifically the control of the polarized distribution of the cell fate adapter protein Miranda. We reveal a step-wise polarization of Miranda in larval neuroblasts and find that Miranda's dynamics and cortical association are differently regulated between interphase and mitosis. In interphase, Miranda binds to the plasma membrane. Then, before nuclear envelope breakdown, Miranda is phosphorylated by aPKC and displaced into the cytoplasm. This clearance is necessary for the subsequent establishment of asymmetric Miranda localization. After nuclear envelope breakdown, actomyosin activity is required to maintain Miranda asymmetry. Therefore, phosphorylation by aPKC and differential binding to the actomyosin network are required at distinct phases of the cell cycle to polarize fate determinant localization in neuroblasts.