Coordinating exit from the cell cycle with differentiation is critical for proper development and tissue homeostasis. Failure to do so can lead to aberrant organogenesis and tumorigenesis. However, little is known about the developmental signals that regulate the cell cycle exit-to-differentiation switch. Signals downstream of two key developmental pathways, Notch and Salvador-Warts-Hippo (SWH), and of myosin activity regulate this switch during the development of the follicle cell epithelium of the Drosophila ovary. Here, we have identified a fourth player, the integrin signaling pathway. We find that elimination of integrin function blocks mitosis-to-endocycle switch and differentiation in posterior follicle cells (PFCs), via regulation of the CDK inhibitor dacapo. In addition, we show that integrin mutant PFCs show defective Notch signalling and endocytosis. Furthermore, integrins act in PFCs by modulating the activity of the Notch pathway, as reducing the amount of Hairless, the major antagonist of Notch, or misexpressing Notch intracellular domain rescues the cell cycle and differentiation defects. Altogether, our findings reveal a direct involvement of integrin signalling on the spatial and temporal regulation of epithelial cell differentiation during development.
Epithelial cells are polarised within the plane of the epithelium, forming oriented structures that have a coordinated and consistent polarity (planar cell polarity, PCP). In Drosophila, at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the ‘core’ or Starry night/Frizzled system. Here, we study the prickle gene and its protein products Prickle and Spiny leg. Much research on PCP has focused on the asymmetric localisation of core proteins in the cell and as a result prickle was placed in the heart of the Starry night/Frizzled system. We investigate whether this view is correct and how the prickle gene relates to the two systems. We find that prickle can affect, separately, both systems; however, neither Prickle nor Spiny leg are essential components of the Dachsous/Fat or the Starry night/Frizzled system, nor do they act as a functional link between the two systems.
Epithelial cells are polarised within the plane of the epithelium, forming oriented structures whose coordinated and consistent polarity (planar cell polarity, PCP) relates to the principal axes of the body or organ. In Drosophila at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the “core” or Stan system. Here we study the prickle gene and its protein products Prickle and Spiny leg. Much research on PCP has focused on the asymmetric localisation of core proteins in the cell and as a result prickle was placed in the heart of the Stan system. Here we ask if this view is correct and how the prickle gene relates to the two systems. We find that prickle can affect, separately, both systems — however, neither Pk nor Sple are essential components of the Ds/Ft or the Stan system, nor do they act as a functional link between the two systems.
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