Every cell in a fly’s wing knows which way is up—and a team wants to know how. The researchers are studying how cells in a growing fruit fly coordinate their internal compasses, a process called planar cell polarity, which is essential for building and maintaining healthy tissues in all animals, including humans. When this coordination fails, it can lead to developmental disorders and diseases such as spina bifida or certain cancers. The team is using live imaging to watch the key molecules—the core planar polarity and Fat/Dachsous pathways—in action inside living fly tissues, then disrupting them to see what breaks. They will also run genetic screens to find missing components and build computational models to test their hypotheses. This is fundamental science: there is no immediate medical application. But understanding how cells align their polarity in space and time could eventually explain why some tissues fail to form correctly, and point toward ways to intervene. Similar work on cell signalling in flies has already revealed mechanisms behind human birth defects and cancer metastasis.
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Coordination of cell polarity in multi-cellular organisms is essential for morphogenesis and maintenance of healthy tissues and yet remains poorly understood due to incomplete knowledge regarding the specific roles of key molecules and how their collective behaviour leads to the emergence of pattern. An understanding of these processes would provide fundamental insights into a range of developmental disorders and disease states. Our approach is to study two conserved mechanisms, the core plana r polarity and Fat/Dachsous pathways, using Drosophila as a model system which provides accessible tissues, sophisticated tools, and negligible genetic redundancy. We will investigate the dynamic behaviour of the pathway components using in vivo live imaging during the process of coordinated cell polarisation. We will ask how this dynamic behaviour is affected by disruption of activity of other pathway components and interacting factors, and also how it is influenced by processes known to be inv olved in symmetry breaking in other contexts such as phosphorylation and intracellular trafficking. This will allow us to determine roles for specific factors in coupling polarity between cells, acting in feedback loops that promote cellular symmetry breaking, and promoting alignment of asymmetry with tissue axes. Our knowledge of the cellular machinery involved will be used to design targeted genetic screens to identify missing factors. Specific hypotheses regarding mechanism will be investigat ed using quantitative computational modelling. The overall aim is a fundamental understanding of how the spatiotemporal interactions of specific proteins and the cellular machinery can lead to coordination of cell polarity in all animals.
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