Role of Notch signalling during neural crest migration

细胞的迁移能力是许多生物过程的基础，从胚胎形成到癌症进展。在胚胎发育过程中，会产生数千种不同的细胞类型，这些细胞必须从原来的位置迁移才能发挥作用。例如，色素细胞出生在胚胎脊髓的顶端，它们从那里迁移并定居在整个身体的皮肤上。在癌症中，转移细胞从原始肿瘤向外迁移是形成继发性肿瘤的原因。这一过程带来了灾难性的后果，90%的癌症患者的死亡都要对此负责。因此，了解控制细胞迁移的机制是生物学和医学的一个主要问题。细胞迁移有三个主要步骤。首先，细胞必须与邻居分离，才能自由移动。其次，他们必须决定去哪里，最后，他们必须认识到他们的旅程何时结束。我的项目的目标是了解控制这些步骤的一组分子。为了研究这些问题，我们将使用神经脊细胞作为模型系统。神经脊细胞在胚胎发育早期就出生了，它们广泛迁移并分化为多种细胞类型(神经元、色素细胞、软骨等)。由于神经脊在胚胎发育过程中形成较早，因此很容易进行直接实验。此外，它们的迁移行为与包括癌细胞在内的其他迁移细胞的许多特征相同，使神经脊细胞成为研究细胞运动的理想系统。在这个项目中，我将研究鱼胚胎中的神经脊迁移。鱼很容易在实验室里生长并产生大量的胚胎。这些胚胎是透明的，使我们能够拍摄神经脊细胞，并实时观察它们如何与邻居连接，它们的形状如何变化，它们如何移动。重要的是，在FISH中，我们可以修改我们认为控制迁移的基因，然后测试这些变化对细胞运动的影响：细胞正常分离吗？细胞形状改变了吗？它们是如何移动的？这些问题的答案将使我们能够决定哪些基因对细胞迁移是重要的。总之，这项研究将使我们更好地了解细胞迁移，我们将了解到，哪些基因控制着这一过程。重要的是，它还可以帮助我们识别癌症治疗的新靶点分子。

The ability of cells to migrate is fundamental for many biological processes, from embryo formation to cancer progression. During embryo development thousands of different cell types are generated, these have to migrate from their original positions to be functional. For example pigment cells are born on top of the embryonic spinal cord, from where they migrate and colonise the skin of the entire body. In cancer, migration of metastatic cells away from the original tumour is responsible for the formation of secondary tumours. This process has catastrophic consequences, being responsible for 90% of deaths of cancer patients. Understanding the mechanisms controlling cell migration is therefore a major question for biology and medicine.Cell migration has three main steps. First, cells have to detach from their neighbours to become free to move. Second, they have to decide where to go and finally, they have to recognise when their journey is over. The objective of my project is to understand which set of molecules control these steps.To study these questions we will use neural crest cells as a model system. Neural crest cells are born early during embryogenesis, they migrate extensively and differentiate in many cell types (neurons, pigments cells, cartilage, etc). Because of their early formation during embryogenesis, neural crest are easily accessible for direct experimentation. Moreover, their migratory behaviour shares many features with that of other migratory cells, including cancer cells, making neural crest cells an ideal system to study cell movement.In this project, I will study neural crest migration in fish embryos. Fish are easy to rise in the laboratory and produce large numbers of embryos. These embryos are transparent, enabling us to film neural crest cells and watch, in real time, how they connect to their neighbours, how their shape changes and how they move. Importantly in fish, we can modify the genes we think control migration and then test the effects of these changes in cell movement: are cells detaching normally? Is cell shape changed? And how do they move? The answers to these questions will allow us to decide which genes are important for cell migration.In conclusion, this study will provide us with a better understanding of cell migration and we will learn, which genes control this process. Importantly, it can also help us to identify new target molecules for cancer therapies.