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

钙粘蛋白 Fat 和 Dachsous 如何控制发育过程中的极化细胞行为？

• 批准号: BB/S007342/1
• 负责人: David Strutt
• 金额: $ 51.01万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS007342%2F1
• 关键词: How; do; cadherins; Fat; Dachsous

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.

组成我们身体组织和器官的细胞通常需要知道左右或前后。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相邻细胞重新排列，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）。如果细胞失去了这种有组织的控制，那么组织的形成和功能就会出现错误，导致出生缺陷。有一些系统可以为细胞提供这种方向信息。一个这样的系统被称为脂肪Dachsous途径。它由两个大的蛋白质组成，它们位于细胞的相对两端，为细胞提供方向。我们不完全了解的是细胞如何“读出”这种脂肪和Dachsous蛋白的不均匀分布，从而导致细胞内的变化。Fat-Dachsous通路在果蝇中得到了广泛的研究，科学家通常使用它来询问细胞如何形成组织的基本问题。果蝇中的脂肪蛋白和Dachsous蛋白与人类中的蛋白相似，因此我们在苍蝇中发现的东西可能对我们了解这些蛋白在人类疾病中的作用具有重要意义。我们将进行实验，以了解细胞如何读取脂肪Dachsous信号，以及这如何影响细胞的行为。具体来说，我们将研究细胞中的蛋白质网络，称为肌动蛋白和微管细胞骨架-纤维网络赋予细胞结构。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如何变化。然后，我们可以将脂肪或Dachsous蛋白质拿走或添加回来，并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对脂肪或Dachsous的分布产生反应，从而引起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蛋白质分布，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需的。

项目成果

Deciphering the roles of cell shape and Fat and Dachsous planar polarity in arranging the

破译细胞形状以及脂肪和达克斯平面极性在排列中的作用

• 发表时间: 2023
• 期刊: MOLECULAR BIOLOGY OF THE CELL
• 影响因子: 3.3
• 作者: Ramirez-Moreno Miguel

How do the Fat-Dachsous and core planar polarity pathways act together and independently to coordinate polarized cell behaviours?

• DOI: 10.1098/rsob.200356
• 发表时间: 2021-03
• 期刊: Open biology
• 影响因子: 5.8
• 作者: Strutt H;Strutt D
• 通讯作者: Strutt D