The Establishment and Maintenance of Centrosome Asymmetry in Neural Stem Cells

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Asymmetric cell division (ACD) is used by stem cells to create diverse cell types while self-renewing the stem cell population. Nested within ACD is the biased segregation of organelles, which carries functional consequences on the functionality of sister cells from ACD. Centrosomes, which are the microtubule organizing centers of cells, are comprised of a pair of centrioles that differ by age and molecular composition. Biased segregation of molecularly distinct centrosomes could provide a mechanism to maintain stem cell fate, induce cell differentiation or both. However, the molecular mechanisms generating molecular and functional asymmetric centrosomes remain incompletely understood. The neural stem cell lineage in the developing Drosophila larval brain (neuroblasts) provide a robust model to address our mechanistic understanding of centrosome asymmetry within the context of ACD. Neuroblasts divide asymmetrically to form one neuroblast, which retains its stemness, and one ganglion mother cell (GMC), which will differentiate and divide once more to form neuronal and glial cells. Here, we show how to utilize Drosophila neuroblasts to study basic cell biology and ACD, and using Drosophila neuroblasts, we show that protein phosphatase 4 (Pp4) is functionally required for centrosome asymmetry.

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Thesis (Ph.D.)--University of Washington, 2025

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