6th Annual Symposium
Physics of Cancer
September 7-9, 2015
|PoC - Physics of Cancer - Annual Symposium|
Anisotropies in adhesion and cytoskeletal organisation induced by mechanical and oxidative stresses contribute to cell delamination in a Drosophila epithelium
Tata Institute of Fundamental Research, Mumbai, India
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The morphogenesis and maintenance of tissues relies on dynamic and heterogeneous cell behaviors. The origin of these heterogeneities and their coordination remain poorly understood. We investigate how heterogeneities and transitions in cell behavior are patterned using the amnioserosa, an active participant during Drosophila dorsal closure as our model and seek to understand the cellular, molecular and physical bases of individual behaviors (both stochastic and collective) and their coordination that ensures the stereotypical dynamics of this tissue.
Cell delamination is a seemingly stochastic cell behavior that resembles an epithelial to mesenchymal transition and results in the extrusion of the cell from the epithelium. Using a combination of approaches including targeted (single cell) genetic and nanoscale laser perturbations, cell biology, 4D live confocal microscopy and quantitative morphological analysis, we find that cell delaminatiion results from differences in the spatial organization of cell-cell adhesion and the actomyosin and microtubule cytoskeleton in the delaminating cell and in its nearest neighbors. These anisotropies are in turn influenced by stochastic fluctuations and asymmetries in physical (geometry and tension) and chemical (metabolic and oxidative stress signalling) cues that we find act both autonomously and non-autonomously to create a local spatial pattern. Our findings are beginning to provide insights into the local control of cell behavior and their influence on the spatial patterning of tissues during morphogenesis. They also provide an explanation for compromised tissue integrity in metabolic and oncological pathologies.