The role of physics in epithelial homeostasis and development.
Doctoral thesis, UCL (University College London).
Developing epithelial tissues are characterised by the disordered cell packing caused by ongoing cell proliferation and changes in tissue size. However, cell packing in adult epithelial tissues exhibits a high level of order, and typically, the apical tissue surface resembles a regular hexagonal lattice of planar polygons. One of the central questions in tissue development concerns the mechanisms which induce cells to repack. The change in packing may transform the tissue into a regular pattern of hexagonal cells, as seen during the refinement of Drosophila M. wing and notum tissue, or it can occur as a mechanism which drives tissue shape change, as seen during embryonal axis elongation during Drosophila convergent extension. We study cell repacking in epithelia effected by the forces that act at the interface between adjacent cells. To this end, we develop a mechanical model of epithelial tissue based on the ideas of the cellular Potts model and building on previous vertex models. Analysing expanding and fixed-size tissues, we find that steady state packing geometries depend on the regularity in the timing of cell divisions. We predict that cells in topologically active epithelia leave the tissue in response to mechanical compression and geometric anisotropy. Through a collaboration with biologists Eliana Marinari and Buzz Baum, we find that such mechanically driven cell delamination indeed occurs in the Drosophila notum. We thus identify a novel process of tissue homeostasis, whereby live cells delaminate from developing epithelium in order to limit overcrowding. Analysing the relation between stable packing geometries and the mechanical parameters, we suggest that an increase in the strength of acto-myosin contractility alone could cause tissue to repack into a regular lattice. Modifying the model to describe polarised acto-myosin localisation, we computationally reproduce cell intercalation and actin cable and rosette formation during convergent extension in Drosophila.
|Title:||The role of physics in epithelial homeostasis and development|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of BEAMS > Faculty of Maths and Physical Sciences > Physics and Astronomy|
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