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Transcriptional responses to FGF signalling during germ layer specification

胚层规范过程中对 FGF 信号传导的转录反应

基本信息

批准号：
BB/D010039/1
负责人：
Harry Isaacs
金额：
$ 52.38万
依托单位：
University of York
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FD010039%2F1
关键词：
Transcriptional responses FGF signalling during

项目摘要

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.

所有有脊椎的动物都以类似的方式发育。尽管青蛙看起来与人类有很大不同，但其胚胎发育中涉及的许多过程和蛋白质非常相似。我们使用非洲爪蟾胚胎来研究早期发育，因为它们产下数百个卵，这些卵很容易在培养皿中受精。产生的大量鸡蛋很重要，因为它们为我们的实验和化学纯化提供了大量材料。此外，胚胎发育非常迅速，仅需三天即可达到游泳蝌蚪阶段。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，从而激活或抑制参与发育的特定蛋白质或基因的功能。我们对一组称为成纤维细胞生长因子 (FGF) 的蛋白质感兴趣。 FGF 存在于所有动物中，在胚胎和成体细胞相互沟通方面发挥着重要作用。这种从一个细胞传递到另一个细胞的信号对于发育非常重要，因为它们参与了单个细胞决定它们在成人中形成什么的过程。 FGF 对于决定特定细胞群是否会形成肌肉、骨骼、肾脏或神经系统等组织特别重要。 FGF 告诉细胞要打开哪些基因，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，FGF 可以告诉胚胎中的细胞变成肌肉。在这种情况下，FGF 信号会告诉细胞开启基因，从而产生肌肉收缩所需的蛋白质。我们已经知道 FGF 信号将激活的一些基因，但我们想了解全部。最新的技术进步意味着我们现在可以尝试识别所有由 FGF 信号开启的基因。我们计划的实验非常简单。我们将采集非常早期的青蛙胚胎样本并刺激这些样本中的 FGF 信号传导。然后，我们将比较这些样本中哪些基因被激活，以及我们没有刺激 FGF 信号传导的样本。这将首次对发育中胚胎中 FGF 信号激活的基因进行大规模观察。研究动物早期发育的人们以及对成年人的身体如何自我维持和修复感兴趣的人们将会对我们的工作感兴趣。这是因为 FGF 参与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制成的蛋白质的性质。我们还将尝试通过过度激活或抑制早期青蛙胚胎中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来建立基于计算机的模型，以了解所有这些基因在发育过程中如何相互作用。最终，这些模型将使我们能够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参与发育的特定基因的后果。