The role of Lgl, aPKC, and Numb in Distinguishing Neural Stem Cells from progenitor cells in Drosophila.

[摘要] Asymmetric cell division is a conserved mechanism for distinguishing cells following mitosis in order to produce two daughter cells with unique functions and characteristics.Significant progress has been made in understanding how proteins at the cell cortex become asymmetrically localized and how determinants function in establishing distinct cell fates.Also, recent studies have shown that cells actively maintain the fate which they initially acquired.My studies utilize clonal analysis and genetic techniques to investigate how this cell polarity and maintenance of cell fate are linked in order to distinguish neural stem cells from progenitor cells in Drosophila.In mitotic neural stem cells (neuroblasts) in fly larval brains, the antagonistic interaction between the polarity proteins Lethal (2) giant larvae (Lgl) and atypical Protein Kinase C (aPKC) ensures self-renewal of a daughter neuroblast and generation of a progenitor cell by regulating asymmetric segregation of fate determinants.In the absence of lgl, increased cortical aPKC activity triggers progenitor cells to revert back into neuroblasts.Additionally, I found that together Lgl and aPKC ensure asymmetric localization and segregation of Numb in the cortex of the mitotic neuroblast.Specifically, aPKC regulates asymmetric localization of Numb via phosphorylation of the previously undefined serines 48 and 52 sites in the novel ACBD3 binding region.However, the phosphorylation status at these two sites does not affect the function of Numb in the progenitor cells.Finally, the ACBD3 binding region exerts neuroblast-specific suppression of Notch signaling by Numb independently of phosphorylation by aPKC.Taken together, my work suggests that mutual antagonism between Lgl and aPKC ensures that Numb properly segregates exclusively into the progenitor cells where Numb maintains limited potential irrespective of the phosphorylation by aPKC.

[发布机构] University of Michigan

[效力级别] Cell Polarity

[关键词] Asymmetric Division;Cell Polarity;Intermediate Neural Progenitor;Neural Stem Cell;Lethal Giant Larvae;Numb;Molecular;Cellular and Developmental Biology;Science;Cellular & Molecular Biology