GSK3 and lamellipodial dynamics in migrating neural crest cells

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Cell movement is extremely important during development of the human body and during every day biological processes. In addition, cell movements become critically necessary during wound healing and when replacing aging tissues. Finally, cell movements influence how far cancer cells can spread in the body. This is a process that is very difficult to study because it is hard to see inside the live body as cells move around. In this proposal, we use an embryonic cell population called the neural crest to study how cells receive and interpret signals from the environment.The neural crest is a very interesting cell population which contributes to all kinds of tissues in humans, including bones of the head, nerves, pigmentation and fat. Although these cells become very different, they are all born in the embryo at the edge of the neural plate. They then have to emerge from the neural tube and migrate through the body, in some cases travelling great distances before settling down. For example, the nerves that control bowel movements must travel to the gut, while correctly becoming nerves. When this goes wrong, the bowels don't work, resulting in Hirschsprung's disease. Because neural crest cells travel throughout the body before they differentiate, they are one of the few normal cell populations that are most similar to metastatic tumour cells. In fact, the neural crest cells sometimes reactivate in later life, and can then form highly invasive cancers such as melanoma, neuroblastoma and glioblastoma.In this project, we are studying the machinery that drives the movement of these cells. We have identified several proteins help the cells to move in a forward direction, but making a broad "footlike" structure that feels its way through surrounding tissues. We want to ask what happens when these proteins are unable to function. Questions include: can the cells reach out and move in the correct direction, can they compensate by using another method of transportation, can they still move as quickly? The answers to these questions will be important for our understanding of how the tissues in the embryo come together and make organs. We will also learn what happens when the process goes wrong (for example, does this cause birth defects) as well as giving us insight into how cancer cells move through the body.