A study of epithelial cell delamination in Drosophila.
Doctoral thesis, UCL (University College London).
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The developmental refinement of an epithelium requires finely balanced rates of growth and cell loss. However, the molecular mechanisms that regulate the achievement of homeostasis, which are likely to be deregulated in tumorigenesis, remain poorly understood. In this work using the fly notum as a model system and laser cutting experiments to test in vivo tissue mechanics, I describe a novel process of live cell delamination that counter-balances tissue growth to ensure the achievement of mechanical equilibrium in the final phases of development. The fly notum is an ideal system to study this type of mechanical buffering since it remains approximately constant in size during the final phases of tissue refinement in development, whilst requiring cell growth, division and cell loss. Individual cells leaving overcrowded regions of the notum by live cell delamination follow a path of progressive junctional and apical area loss, in a 2-step mechanism that is independent of cell death. Cells first undergo serial junctional loss, leading to a cell with a small apex and few sides, followed by Myosin-II driven apical extrusion. This process of live cell delamination can be recapitulated by a simple vertex model of epithelial mechanics, where pressure is relieved as cells leave the tissue via a series of stochastic neighbor exchange events. These findings suggest that crowding-induced live cell delamination is a generic mechanism that buffers epithelia against variations in growth. This has important implications for our understanding of homeostasis and its deregulation in cancer, as well as for cancer cell invasion and metastasis.
|Title:||A study of epithelial cell delamination in Drosophila|
|Open access status:||An open access version is available from UCL Discovery|
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|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > MRC/UCL Lab for Molecular Cell Biology|
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