View Program - 63rd Annual Drosophila Research Conference

Asymmetric cell division (ACD) is an evolutionarily conserved process where proteins, organelles, and mRNAs are unequally partitioned between daughter cells. This maintains the stem cell population, where progenitor cells undergo ACD to produce a self-renewing stem cell and a differentiating daughter cell. Organelles, such as centrosomes, can be partitioned asymmetrically between daughter cells, and this is observed in many diverse cell types. In Drosophila neural stem cells, called neuroblasts, the differentiating ganglion mother cell receives the older mother centrosome, while the renewing neuroblast receives the younger daughter centrosome. This biased inheritance is determined by differences in molecular identity, which is mediated by the phosphorylation activity of Polo kinase. Preliminary data has implicated the involvement of protein phosphatase 4 (PP4) in this cascade, and the extent of PP4’s molecular involvement in this process is not fully understood. These molecular identities are speculated to impact the other factors during ACD. Additionally, centrosomes retain distinct clusters of mRNA, and this retention is theorized to be facilitated by the molecular identity of the centrosome. However, the spatiotemporal mechanisms that regulate centrosome asymmetry and its functional impact are unknown. I hypothesize that (1) dephosphorylation of cytoskeletal proteins, such as gamma-tubulin, contribute to the establishment and maintenance of centrosome asymmetry, and (2) biased mRNA localization is dependent on centrosome asymmetry. To address these hypotheses, I will utilize fluorescent in vivo imaging and novel optogenetic methods to elucidate the spatiotemporal regulation and functional importance of centrosome asymmetry. These experiments will reveal the regulation of this process within the context of ACD, which will broaden our understanding of its importance in other processes, such as stem cell differentiation and the onset of cancer.

The Establishment and Maintenance of Centrosome Asymmetry in Neural Stem Cells