Transcriptional responses to FGF signalling during germ layer specification

所有有脊椎的动物都以相似的方式发育。尽管青蛙看起来与人类非常不同，但它们胚胎发育的许多过程和蛋白质都非常相似。我们使用爪蟾胚胎来研究早期发育，因为它们会产下数百个卵，这些卵很容易在培养皿中受精。大量生产的鸡蛋很重要，因为它们为我们的实验和化学净化提供了大量的材料。此外，胚胎发育非常迅速，仅在三天内就能发育成蝌蚪。胚胎相当大（直径1毫米），这意味着它们可以被注射化学物质，激活或抑制参与发育的特定蛋白质或基因的功能。我们对一组被称为成纤维细胞生长因子（FGFs）的蛋白质感兴趣。FGFs存在于所有动物中，在胚胎和成体细胞之间的相互交流中发挥着重要作用。这种从一个细胞传递到另一个细胞的信号在发育过程中很重要，因为它们参与了单个细胞决定它们在成年细胞中形成的过程。在决定一组特定细胞是否会形成肌肉、骨骼、肾脏或神经系统等组织方面，FGFs尤为重要。FGFs告诉细胞哪些基因可以开启，因为每个基因都编码一种蛋白质，这最终会告诉细胞要制造哪些蛋白质。例如，FGFs可以告诉胚胎中的细胞变成肌肉。在这种情况下，FGF信号告诉细胞开启基因，使肌肉收缩所需的蛋白质得以产生。我们已经知道FGF信号会激活的一些基因，但我们想知道所有的基因。最近的技术进步意味着我们现在可以尝试识别所有由FGF信号激活的基因。我们计划的实验很简单。我们将采集非常早期的青蛙胚胎样本，并在这些样本中刺激FGF信号。然后，我们将比较在这些样本中哪些基因被激活，而在没有刺激FGF信号的样本中，哪些基因被激活。这应该是第一次对发育中的胚胎中FGF信号激活的基因进行大规模观察。我们的工作将对研究动物早期发育的人以及对成年人身体如何维持和修复自己感兴趣的人感兴趣。这是因为FGFs参与了成人和胚胎的许多过程。一旦我们确定了FGF靶基因，这本身就是非常有用的信息，我们将开始研究由这些基因组成的蛋白质的性质。我们还将试图通过在早期青蛙胚胎中过度激活或抑制这些蛋白质的产生来发现这些蛋白质在发育过程中的作用。我们还计划利用从这些实验中获得的大量信息，建立基于计算机的模型，研究所有这些基因在发育过程中如何相互作用。最终，这些模型将使我们更好地理解细胞在包括人类在内的所有动物的发育过程中需要做出的决定。它们还可以让我们预测抑制或激活与发育有关的特定基因的后果。

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.