Transcriptional responses to FGF signalling during germ layer specification

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All animals with backbones develop in similar ways. Although frogs would seem to be very different from humans, many of the processes and proteins involved in the development of their embryos are very similar. We use Xenopus frog embryos to study early development because they lay many hundreds of eggs which can easily be fertilized in a Petri dish. The large number of eggs produced is important because they provide lots of material for our experiments and chemical purifications. Furthermore, the embryos develop very rapidly and reach the swimming tadpole stage in just three days. The embryos are quite large (1 mm diameter) which means they can be injected with chemicals that either activate or inhibit the function of particular protein or gene involved in development. We are interested in a group of proteins known as the fibroblast growth factors (FGFs). FGFs are found in all animals and play an important role in allowing cells within the embryo and adult to communicate with each other. Such signals passing from one cell to another are important in development because they are involved in the process by which individual cells decide what they will form in the adult. FGFs are particularly important in the decision of whether a particular group of cells will form tissues such as muscle, bone, kidney or the nervous system. The FGFs tell a cell which genes to turn on and because each gene codes for a protein, this ultimately tells a cell which proteins to make. For example, FGFs can tell cells in the embryo to become muscle. In this situation the FGF signal tells a cell to turn on genes which allow the production of proteins needed for a muscle to contract. We already know some of the genes that FGF signals will activate but we would like to know them all. Recent advances in technology mean that we can now attempt to identify all those genes which are turned on by FGF signals. The experiments that we plan are very simple. We will take samples of very early frog embryos and stimulate FGF signalling in these samples. We will then compare which genes are activated in these samples versus samples in which we have not stimulated FGF signalling. This should for the first time give a large scale view of the genes that are activated by FGF signals in the developing embryo. Our work will be of interest to people studying the early development of animals and people interested in how the bodies of adults maintain and repair themselves. This is because the FGFs are involved in many processes in the adult as well as the embryo. Once we have identified the FGF target genes, which in itself is very useful information, we will begin to investigate the nature of the proteins made from these genes. We will also attempt to discover what these proteins do during development by over activating or inhibiting their production in the early frog embryo. We also plan to use the large amounts of information gained from these experiments to make computer based models of how all these genes interact with each other during development. Ultimately these models will allow us to understand better the decisions that cells need to make during the development of all animals including humans. They might also allow us to predict the consequences of inhibiting or activating a particular gene involved in development.