Interstitial Cells in the Musculature of the Gastrointestinal Tract: Cajal and Beyond

Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component (electrical slow waves of depolarization) of the smooth musculature and are involved in neurotransmission. By integration of ICC functions, substantial progress has been made in our understanding of the neuromuscular control of gastrointestinal motility, opening novel therapeutic perspectives. In this article, the ultrastructure and light microscopic morphology, as well as the functions and the development of ICC and of neighboring fibroblast-like cells (FLC), are critically reviewed. Directions for future research are considered and a unifying concept of mesenchymal cells, either KIT positive (the "ICC") or KIT negative "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells is not likely to be restricted to the gastrointestinal musculature.