GDNF and development of the intestinal nervous system

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Animal models show that the intestine is quite short at birth, but reaches several feet in length in the young adult. In the growing intestine, smooth muscle cells increase in number and are responsible for contraction or relaxation that will propel the intestinal contents appropriately for digestion and absorption of nutrients. These cells require the control of the millions of neurons in the intestinal nervous system in order to do this. These neurons are present at birth and do not increase in number at all, but like neurons in the brain or spinal cord, they must extend long thin processes (axons) to act on other cells by the release of chemicals called neurotransmitters. Working with students that are learning valuable skills in scientific methods, I will study how and why do they do this in the growing intestine. Together, we will investigate the factors that keep this population of nerve cells alive, and that cause them to extend their axons to the right places. In the early embryo, long before birth, studies show that the neurons enter the tube that would become the intestine through following factors that it was making. Called neurotrophins, these can influence target cells only when they make the right molecules that can detect them. We will study whether these same factors continue to be made after birth, by cells in the intestinal wall, and whether neurons continue to be able to respond to them. The major neurotrophin is glia cell line derived neurotrophic factor (or GDNF) since it was first found in glial cells, but is now known to be made by other cell types. We will study how and when it is made, and how affects neurons through use of tissue culture, which is simply a way of keeping cells outside the body for observation and manipulation. This could reveal how the growing intestine makes sure that its vitally important nervous system "grows" right along with it - constantly changing its wiring to be able to control the muscle cells that are so important to intestinal function. This project will increase our knowledge of the natural world, and add to Canada's knowledge-based work force, providing technologists for support of research endevours in many areas and training graduate students that may continue in academia or in industry.