How do the cadherins Fat and Dachsous control polarised cell behaviours during development?

构成我们身体组织和器官的细胞经常需要分辨左右或前后。它们需要这种方向信息，因为当组织形成时，细胞需要向同一方向移动或与邻近细胞重新排列以产生正确形状的器官。此外，为了某些器官（如肺）的正常功能，细胞都需要产生指向同一方向的纤毛（细胞表面的毛发）。如果失去对细胞的这种有组织的控制，那么组织的形成和功能就会出现错误，从而导致出生缺陷。有一些系统可以向细胞提供这种定向信息。其中一个系统被称为Fat-Dachsous通路。它由两个大的蛋白质组成，它们位于细胞的两端，为细胞提供方向。我们不完全了解的是，细胞是如何“读出”这种脂肪和达克斯蛋白的不均匀分布，从而导致细胞内的变化的。Fat-Dachsous通路在果蝇中得到了广泛的研究，科学家们通常用它来研究细胞如何形成组织的基本问题。果蝇中的脂肪蛋白和Dachsous蛋白与人类中的相似，所以我们在果蝇中的发现可能对我们理解这些蛋白质与人类疾病的关系有重要意义。我们将进行实验，以了解细胞如何读出Fat-Dachsous信号，以及这如何影响细胞的行为。具体来说，我们将研究细胞中被称为肌动蛋白和微管细胞骨架的蛋白质网络，它们是赋予细胞结构的纤维网络。我们将使用显微镜技术对蛋白质进行成像，使我们能够测量蛋白质的数量以及它们是如何变化的。然后，我们可以将Fat或Dachsous蛋白取出或添加回来，然后观察蛋白质或细胞行为方式的变化。我们还将研究新的蛋白质，我们认为这些蛋白质可能会对脂肪或Dachsous的分布做出反应，从而导致肌动蛋白和微管网络的变化。通过我们的实验，我们将了解细胞如何理解脂肪/Dachsous蛋白分布，从而导致一系列细胞行为，这些行为是组织正确形式和功能所必需的。

The cells that make up the tissues and organs of our body often need to know left from right or front from back. They need to have this directional information as when tissues are forming cells need to move in the same direction or rearrange with their neighbours to produce organs of the correct shape. Also, for the correct function of some organs, such as the lungs, cells all need to produce cilia (hairs on the surface of cells) that point in the same direction. If this organised control of cells is lost then mistakes in the formation and function of tissues can occur leading to birth defects.There are systems in place that provide this directional information to cells. One such system is called the Fat-Dachsous pathway. This consists of two large proteins that are localised at opposite ends of the cell providing a direction to the cells. What we don't fully understand is how cells "read out" this uneven distribution of Fat and Dachsous proteins resulting in changes within the cell.The Fat-Dachsous pathway has been extensively studied in the fruit fly, which is commonly used by scientists to ask basic questions about how cells behave to form tissues. The Fat and Dachsous proteins in the fruit fly are similar to those in humans, so what we find out in flies may have significance for our understanding of these proteins in human disease. We will carry out experiments to understand how cells read out Fat-Dachsous signals and how this influences how cells behave. Specifically we will look at networks of proteins in the cells called the actin and microtubule cytoskeletons - networks of fibres that give cells their structure. We will image proteins using microscopy techniques that allow us to measure amounts of proteins and how they are changing. We can then take Fat or Dachsous protein away or add it back and look at changes in the way proteins or cells behave. We will also look at new proteins that we think may respond to the distribution of Fat or Dachsous to cause changes in the actin and microtubule networks. Through our experiments we will understand how Fat/Dachsous protein distributions are understood by cells, leading to a range of cell behaviours, that are needed for the correct form and function of tissues.