Principles of neural lumen morphogenesis in vivo

在脊椎动物胚胎的发育过程中，许多内部器官都是由一个中空的中心(称为管腔)构成的，例如大脑和脊髓、肠道、血管、部分肾脏等。因此，管腔的形成是胚胎生命中一个非常基本的过程。我们对这一过程的了解非常有限，事实上，我们掌握的大部分信息并不是来自于对真实胚胎的研究，而是试图研究在塑料培养皿中特殊条件下生长的细胞和组织中的这一过程。这种对真实胚胎外细胞的研究是有价值的，但不一定能完全代表真实动物体内实际发生的正常环境和过程。我们正在使用一个简单的动物系统来研究真实胚胎的管腔形成。为此，我们使用的鱼胚胎具有透明的巨大优势，因此整个胚胎可以放在显微镜下，以便在自然环境中以高分辨率研究单个细胞的行为。我们将进行的主要实验旨在告诉我们，所有细胞中称为中心体的一小部分是否是组织斑马鱼大脑和脊髓管腔形成过程的关键特征。我们之前的实验表明，中心体是这一过程中的关键角色，但我们之前还无法对这一想法进行实验测试。我们工作的第二个目标是测试我们从鱼类大脑和脊髓发育研究中学到的原理在其他与人类更接近的动物的脊髓发育过程中也很重要。为此，我们将研究小鼠胚胎和鸡胚胎脊髓下端的发育。已经证实，在鱼类脊髓和小鼠和鸡脊髓发育的管腔形成过程中，细胞的基本组织有一些相似之处，但几乎没有关于小鼠和鸡在分子水平上的信息(即涉及哪些基因和蛋白质)。我们在鱼类上的工作让我们很好地了解了哪些基因和蛋白质在小鼠和小鸡中可能是重要的，因此我们将详细研究这些基因和蛋白质，以便更好地了解脊椎动物胚胎中的这些基本过程。从长远来看，我们的工作将与人体组织修复和替换相关，因为我们的知识将帮助重建受损组织，方法是鼓励患者进行修复，或者首先在培养皿中设计复杂组织，以便将该组织移植到自己的组织或器官受损的患者体内。

During development of vertebrate embryos many of the internal organs are built with a hollow centre (called the lumen), for example the brain and spinal cord, the intestines, blood vessels, parts of the kidneys, etc. Lumen formation is thus a very fundamental process during embryo life. Our understanding of how this process works is very limited and in fact most of the information that we have is derived not from studying real embryos but from trying to study this process in cells and tissues grown under special conditions in plastic petri dishes. Such studies on cells outside the real embryos is valuable but is necessarily not fully representative of the normal environment and processes that actually take place in real animals. We are using a simple animal system to study lumen formation in real embryos. For this we use fish embryos that have the huge advantage of being transparent and therefore the whole embryo can be placed under a microscope in order for the behaviour of individual cells to studied at high resolution in their natural environment. The main experiments we will carry out are designed to tell us whether a small component of all cells called the centrosome is a key feature in organising the process of lumen formation in the zebrafish brain and spinal cord. Our previous experiments have suggested that the centrosome is a key player in this process, but we have not previously been able to test this idea experimentally.The second aim of our work is designed to test the idea that the principles we have learnt and are learning from our studies of fish brain and spinal cord development are also important during spinal cord development in other animals more closely similar to humans. For this we will study the development of the lower end of the spinal cord in mice embryos and chicken embryos. It is already established that there are some similarities in the basic organisation of cells during lumen formation in fish spinal cord and mouse and chick spinal cord development, but there is almost no information for mice and chick at the molecular level (i.e. what genes and proteins are involved). Our work in fish gives us a good idea of which genes and proteins might be important in mice and chick and we will therefore study these in detail in order to better understand these fundamental processes in vertebrate embryos. In the long term our work will be relevant to human tissue repair and replacement as our knowledge will help rebuild damaged tissues either by encouraging repair in a patient or by engineering a complex tissue first in a petri dish in order for that tissue then to be transplanted into a patient whose own tissue or organ has been damaged.