Authors: Jacob Malin; Christian Rosa-Birriel; Victor Hatini
Affiliation: Tufts University School of Medicine, Boston, MA
Keywords: o. tissue growth and remodeling; f. eye disc
Epithelial remodeling relies on modulation of mechanical forces that alter the shape and the relative arrangement of cells. In the Drosophila pupal retina, remodeling is dependent on the repeated pulsed contraction and expansion of cell-cell contacts at the level of adherens junctions (AJs). While actomyosin network assembly controls contraction, branched F-actin network assembly controls expansion. Our goal is to uncover mechanisms that control the pulsatile dynamics of the two networks and coordinate their activities. We previously found that levels of the phosphoinositide PI(3,4,5)P3 (PIP3) increase during contact expansion and decrease during contraction. This result suggests that PIP3 activates the WAVE regulatory complex (WRC) to control F-actin branching and protrusive membrane dynamics that drive expansion. To examine the system further, we investigated the role and localization of the phosphatase and tensin homolog (Pten) that hydrolyzes PIP3 to PI(4,5)P2 (PIP2), and separately phosphoinositide 3-kinase (PI3K), the enzyme that phosphorylates PIP2 to PIP3. We find that Pten localizes to AJs and accumulates dynamically during both expansion and contraction. The dynamic localization of PI3K is still being investigated. In pten mutant eyes, the dynamics of PIP3 and of protrusive and contractile effectors are disrupted and cell-cell contacts are shortened or lost altogether. Loss of pten and constitutive activation of PI3K produce similar phenotypes, and PI3K depletion induces related phenotypes. Overall, our findings suggest that the cyclical production and hydrolysis of PIP3 is central to the control and coordination of contractile and protrusive dynamics. PIP3 has been previously implicated in controlling actomyosin contractility and endocytosis in epithelial remodeling. Our findings suggest that PIP3 turnover, rather than overall PIP3 levels, is required to fine-tune contractile and protrusive dynamics that shape this epithelium during development.