Physiopathology of the enteric nervous system and the interstitial cells in gut motility: morphological, molecular and functional approaches
Interstitial cells of Cajal (ICC) are involved in the control of gut motility. They present rhythmic variations of their membrane potential and constitute electrically coupled networks that assure the spatio-temporal organization of slow waves of depolarization, also called pacemaker component of the gut smooth muscle. ICC are also involved in the transmission of the nerve input to the smooth muscle and play a role of mechanosensors.
The tyrosine kinase receptor KIT is required for the development of ICC and the KIT-immunoreactivity allows identifying ICC by immunohistochemistry. Alterations of ICC have been reported in several situations pathological conditions both in animal models and in human. Oncogenic mutations of KIT are encountered in a majority of gastrointestinal stromal tumours for which targeted therapies are developed actively. Our main goals are on one hand to investigate the contribution of ICC and other types of interstitials cells to the pathophysiology of gastrointestinal motility in mouse models and human diseases and on the other hand identify alterations of the gene expression profile and signal transduction pathways induced in ICC by KIT oncogenic mutants, in in-vitro and in-vivo models and in human GIST.