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

转移是指癌细胞从原来的肿瘤转移到新的宿主组织，在那里肿瘤细胞增殖并产生继发肿瘤的过程。大多数由癌症引起的死亡取决于这种转移过程，而不是原发肿瘤。这种细胞分散过程的分子基础尚不完全清楚。神经嵴是一种胚胎细胞群，起源于胚胎的背侧区域，从那里分散并定植在胚胎的许多组织中，这个过程被比作肿瘤细胞的转移。本项目拟对正常胚胎发育过程中神经嵴细胞的分散进行分析。我们提出了一种基于接触抑制的新机制。简而言之，当两个细胞相遇时，它们停止迁移并远离彼此。我们建议研究控制细胞间相互作用和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，因为它们很容易进行实时成像，而从青蛙胚胎中提取的体外培养的神经嵴则很容易操作。这些结果将帮助我们了解人类疾病（如癌症和其他疾病）的分子和发育原因，从长远来看，可能会产生新的诊断工具。

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.