Start Small: A Model for Tissue-wide Planar Cell Polarity without Morphogens
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Planar cell polarity (PCP) is an important patterning mechanism in both vertebrates and invertebrates by which cells coherently polarize along the apical surface of the epithelium. This patterning mechanism acts upstream of many developmental processes, such as oriented growth, division, cell movements and orientation of body hairs. While various models have been proposed to explain PCP patterning, all rely on persistent global cues/gradients to obtain global orientation of large tissues. However, recent experimental work has shown that this process can happen independently of such global cues, challenging the current paradigm. In this work, we developed a new model for PCP using the Cellular Potts modelling framework to investigate the conditions under which global tissue orientation can be achieved without a tissue spanning morphogen. We found that a combination of a local boundary signal, a small initial tissue size and uniform proliferation can effectively establish long-range polarity without the need for global cues. We also investigated the impact of cell division planes and growth rates on final patterning. Finally, we compared the cell-autonomous and cell non-autonomous versions of our PCP model, as found in flies and mice, and found that the latter offers more robust patterning outcomes in the absence of gradients.
Author summary
Cells must coordinate the spatial organization of certain proteins inside them to produce aligned structures like body hairs and cilia across large distances in various organisms. This polarity of cells is also important to provide directionality for several key events during animal development. It was widely assumed that a graded signal acting across the tissue provides the global cue for the cells to attain this long-range alignment. However, the identity and existence of this global cue have recently been challenged by new experimental findings. In this work we developed a new computational model showing how coherent tissue polarity can emerge from simple, local rules in the absence of a global tissue-spanning signal. Our model proposes a mechanism where local signals polarize a small initial group of cells, and their subsequent proliferation extend this initial alignment across large scales. We extensively tested our model under different conditions and show that this proposed mechanism provides a reliable recipe for the generation of large-scale tissue polarity without the need for global signals.
