A Mouse Model For Studying Talpid3 and Its Role in Hedgehog Signalling

One of the biggest challenges in biology is to understand how a single cell, the fertilised egg, gives rise to organised arrays of cells and tissues and how all the different parts of the body develop in the right places. Recently we have discovered a new gene that is essential for proper development of the embryo. This stemmed from studying an inherited condition in chickens in which the embryos have many defects and die before development is complete. Further work in chick embryos revealed that this gene is required for responding to a cell-cell signalling molecule that controls the development of many parts of the embryo including the limb, brain and face. The cell-cell signalling molecule has also been associated with tumours. Now we have identified the gene responsible for producing the embryonic defects in the mutant chicken embryos, we wish to understand how the protein it encodes works. There are related human and mouse genes. In this project we wish to make mouse models in which we inactivate the related gene either in all the cells of the embryo or specifically in the developing limb. We will also generate embryos that are deficient both in this gene and also other genes in the hedgehog pathway so that we can work out how the genes interact. This will provide one route to exploring the function of the gene and the protein it encodes. Embryos from the mouse models can be frozen down and thus also create a long term resource for studying a crucial cell-cell signalling pathway in development.