Principles of neural lumen morphogenesis in vivo

点击翻译按钮获取中文摘要

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.