The Neural Crest as a new paradigm to study Contact inhibition of Locomotion in vivo: role of Wnt and Ephrin signalling

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Metastasis is the process by which cancer cells disperse from the original tumour and move away to colonize a new host tissue, where the tumor cells proliferate and generate a secondary tumor. Most of the deaths caused by cancer are dependent on this metastatic process and not on the primary tumor. The molecular bases of this cell dispersion process are not completely understood. Neural Crest is an embryonic population of cells originated in the dorsal region of the embryo from where it disperse and colonize many tissues of the embryo, in a process that has been likened to metastasis of tumor cells. In this project we propose to analyze the dispersion of neural crest cells during normal embryonic development. We propose a new mechanism for this process based in Contact Inhibition. Briefly, when two cells meet they stop migrating and move away from each other. We propose to study the chemical signals that control the interaction and the response of this repulsive reaction between cells. We will analyze the migration of the neural crest in live fish embryos as they are very accessible for live imaging and in neural crest cultured in vitro taken from frog embryos as they are very easy to manipulate.The results will help us to understand the molecular and developmental causes underlying human disease, such as cancer and others, and in the longer term is likely to lead to new diagnostic tools.