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

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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.