Understanding how nNOS signaling in the gut influences the development, maintenance and function of interstitial cells of Cajal.

Loss of nerve cells is seen across a number of different gut diseases. Some of the most common of these diseases are Achalasia, Gastroparesis and Diabetes. In these conditions, loss of a particular type of nerve cell, NOS1 nerves, which are important for relaxation of the gut, causes disease. In these diseases another type of cell called interstitial cells of Cajal or ICC is also lost. These ICC cells are important in controlling the gut, including influencing how nerve cells communicate with gut muscles. Their loss causes problems with the movement of substances along the gut resulting in severe symptoms. As both of these cells are lost in disease it appears they might communicate to each other in development. This project will look at whether specific loss of NOS1 nerve cells can change the behaviour of ICC. This will be important for our understanding of normal gut behaviour and disease.