Role of Notch signalling during neural crest migration

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The ability of cells to migrate is fundamental for many biological processes, from embryo formation to cancer progression. During embryo development thousands of different cell types are generated, these have to migrate from their original positions to be functional. For example pigment cells are born on top of the embryonic spinal cord, from where they migrate and colonise the skin of the entire body. In cancer, migration of metastatic cells away from the original tumour is responsible for the formation of secondary tumours. This process has catastrophic consequences, being responsible for 90% of deaths of cancer patients. Understanding the mechanisms controlling cell migration is therefore a major question for biology and medicine.Cell migration has three main steps. First, cells have to detach from their neighbours to become free to move. Second, they have to decide where to go and finally, they have to recognise when their journey is over. The objective of my project is to understand which set of molecules control these steps.To study these questions we will use neural crest cells as a model system. Neural crest cells are born early during embryogenesis, they migrate extensively and differentiate in many cell types (neurons, pigments cells, cartilage, etc). Because of their early formation during embryogenesis, neural crest are easily accessible for direct experimentation. Moreover, their migratory behaviour shares many features with that of other migratory cells, including cancer cells, making neural crest cells an ideal system to study cell movement.In this project, I will study neural crest migration in fish embryos. Fish are easy to rise in the laboratory and produce large numbers of embryos. These embryos are transparent, enabling us to film neural crest cells and watch, in real time, how they connect to their neighbours, how their shape changes and how they move. Importantly in fish, we can modify the genes we think control migration and then test the effects of these changes in cell movement: are cells detaching normally? Is cell shape changed? And how do they move? The answers to these questions will allow us to decide which genes are important for cell migration.In conclusion, this study will provide us with a better understanding of cell migration and we will learn, which genes control this process. Importantly, it can also help us to identify new target molecules for cancer therapies.