Abstract:
A number of stem cells in Drosophila and mammalian systems are partially polarised epithelial cells that have a lateral and basal domain but no apical domain. As a result of their differentiation, an apical domain develops, resulting in a completely polarised epithelial cell. Signaling and metabolic processes combine to control stem cell differentiation. The suppression of the EGFR signaling pathway is coincident with the apical domain formation in Drosophila follicle stem cells and intestinal stem cell differentiation. Previous research has demonstrated that the lack of the mitochondrial fission protein Drp1 results in abnormal EGFR and Notch signaling as well as the loss of follicle cell differentiation. We have attempted an analysis of the role of mitochondrial dynamics in regulating mitochondrial activity and epithelial polarity in follicle cell differentiation. We have found that loss of Drp1 leads to the presence of follicle cells in multiple layers. This is not seen in the depletion of mitochondrial fusion protein Opa1. Multilayering is coincident with a cytoplasmic accumulation of EGFR signaling component ERK and loss of apical polarity protein aPKC. Interestingly, this loss of apical polarity is regulated by levels of reactive oxygen species (ROS). An increase in ROS by depletion of SOD2 and Catalase leads to mitochondrial fragmentation and suppression of apical polarity defect in Drp1-depleted follicle cells similar to Opa1. We find that EGFR signaling pathway activation with ERK inhibits apical polarity in Drp1 depleted follicle cells. Further, mitochondrial fragmentation and an increase in ROS lead to apical polarity and Notch-mediated differentiation in Drp1 depleted follicle cells. Our studies implicate an important interaction between signaling, mitochondrial activity in the form of ROS, and apical polarity formation during differentiation in Drosophila follicle cells.
