A mouse model for studying talpid3 and its role in hedgehog signalling

生物学中最大的挑战之一是了解单个细胞，即受精卵，如何产生有组织的细胞和组织阵列，以及身体的所有不同部分如何在正确的地方发育。最近，我们发现了一种新的基因，它对胚胎的正常发育至关重要。这源于研究鸡的一种遗传条件，其中胚胎有许多缺陷，并在发育完成之前死亡。对鸡胚胎的进一步研究表明，这种基因是对细胞间信号分子做出反应所必需的，这种分子控制着胚胎的许多部分，包括四肢、大脑和脸部的发育。细胞间信号分子也与肿瘤有关。现在我们已经确定了突变鸡胚胎中导致胚胎缺陷的基因，我们希望了解它编码的蛋白质是如何工作的。有相关的人类和小鼠基因。在这个项目中，我们希望制作小鼠模型，在这些模型中，我们将相关基因植入胚胎的所有细胞中，或者专门植入发育中的肢体中。我们还将培育出这种基因和刺猬途径中其他基因都有缺陷的胚胎，这样我们就可以弄清楚这些基因是如何相互作用的。这将为探索该基因及其编码的蛋白质的功能提供一条途径。来自小鼠模型的胚胎可以被冷冻下来，从而也为研究发育中关键的细胞-细胞信号通路创造了长期资源。

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.