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Role of Notch signalling during neural crest migration

Claudia Linker

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Medical Research Council (MRC)
Cell migration is essential for many biological processes such as embryogenesis, wound healing, and tissue homeostasis. In cancer, cell migration plays a critical role during tumour metastasis and is responsible for 90% of deaths of these patients. Despite its importance, it remains one of the most poorly understood aspects of cancer pathogenesis. Because neural crest cells undergo extensive migration in the embryo and share numerous characteristics with metastatic cells, they represent an important model system for studying cell migration. Although neural crest and cancer cell migration have historically been considered from the perspective of single cells moving independently, metastatic cells are frequently found migrating in groups, a process known as collective cell migration. Importantly, collective cell migration endows cancer cells with a higher capacity to disseminate and increased efficiency of metastasis. The aim of this project is to investigate aspects of collective neural crest migration in zebrafish embryos, focusing on the role that the Notch pathway plays in this process. My preliminary data suggest an important role for Notch signalling in neural crest migration. The proposed experiments will expand upon these preliminary results by combining the power of genetics, offered by zebrafish transgenic lines, with live cell imaging and the generation of new tools to study single genetically altered cells in vivo. These approaches will provide a detailed molecular and cellular analysis of neural crest migration. Given the importance of cell migration in tissue homeostasis and its implication in many types of cancers, our findings in neural crest cells will shed light on the mechanism of metastasis and may unveil novel targets for cancer therapies.

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