A study of epithelial cell delamination in Drosophila
2011
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.
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