Normal motility of the gastrointestinal tract is reliant on complex patterns of smooth muscle contraction and the coordinated action of the enteric nervous system, smooth muscle cells and interstitial cells of Cajal. Developmental defects affecting the formation or proper functioning of one of these components, result in variable degrees of abnormal motility, and are the basis of intestinal neuromuscular disorders. In this project, we focus on the study of the smooth muscle to understand the mechanisms underlying intestinal myopathies, such as megacystis microcolon intestinal hypoperistalsis and congenital short bowel syndrome.
This project has three main objectives:
1) To determine how the human intestinal smooth muscle develops during embryogenesis.
2) To identify key components required for smooth muscle contraction and understand how this process occurs.
3) To apply the knowledge gathered to develop a new therapeutic approach for treating intestinal disorders arising from abnormal smooth muscle contraction.
The results obtained will bring new insights into the development and functioning of the smooth muscle, and its contribution to the pathogenesis associated with intestinal myopathies. Moreover, we will develop a system that can be used to check the efficiency and applicability of genetic correction for the treatment of intestinal motility disorders in general. This may ultimately lead to improved management and quality of life of patients affected by such disorders.