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

转移是癌细胞从原始肿瘤分散并移走以定殖到新的宿主组织的过程，其中肿瘤细胞增殖并产生继发性肿瘤。大多数由癌症引起的死亡都依赖于这种转移过程，而不是原发性肿瘤。这种细胞分散过程的分子基础尚未完全了解。神经嵴是起源于胚胎背侧区域的胚胎细胞群，它在胚胎的许多组织中分散和定殖，其过程类似于肿瘤细胞的转移。在这个项目中，我们建议分析正常胚胎发育过程中神经嵴细胞的分散。我们提出了一个新的机制，这个过程的基础上接触抑制。简单地说，当两个细胞相遇时，它们停止迁移并彼此远离。我们建议研究控制细胞间相互作用和这种排斥反应的化学信号。我们将分析活鱼胚胎中神经嵴的迁移，因为它们非常容易进行实时成像，并在青蛙胚胎中体外培养的神经嵴中进行分析，因为它们非常容易操作。结果将有助于我们了解人类疾病的分子和发育原因，如癌症和其他疾病，从长远来看，可能会导致新的诊断工具。

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.