Study of asymmetric division and cell polarity generating cellular diversity

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The asymmetric cell division is a basic process to create cell diversity and plays crucial roles in neural development. In the developing central nervous system of Drosophila, neural stem cells called neuroblasts (NB) divide to produce a chain of sister cells, ganglion mother cells (GMC). The transcription factor Prospero (Pros), a determinant of neuronal cell fates, localizes to the basal cell cortex in NBs at mitosis and segregate asymmetrically into the GMC which buds off from the basal side of the NB.In this study, we focused on the roles of asymmetric divisions in neural development and discovered the following four findings.1. Miranda (Mira) was identified as a factor that binds Pros to direct it to the GMC.Mira basally localizes tethering Pros protein to the basal cortex at the NB mitosis ; this protein complex is subsequently partitioned to the GMC.Shortly after cytokinesis, Pros dissociates from Mira into the nucleus whereas Mira disappears.2. pros mRNA is also known to segregate asymmetrically to the GMC.pros mRNA localization in the NB depends on the RNA binding protein Staufen, which is itself localized asymmetrically at mitosis. We have found that mira function is also necessary for Staufen localization. Mira thus plays a central role for the unequal segregation of Pros protein, Staufen and pros RNA during NB divisions.3. In the absence of Mira, GMCs are not able to express genes that are necessary for progeny neurons to acquire correct identities. Mira thus creates intrinsic differences between NBs and GMCs that later manifest themselves in the divergent developmental paths.4. Pros and Staufen to the basolateral cortex in dividing epithelial cells that express the three proteins prior to neurogenesis, suggesting that the epithelial cell and the NB of epithelial origin share a molecular machinery creating cellular asymmetry.