Interstitial cells of Cajal: a new perspective on smooth muscle function.

Interstitial cells of Cajal (ICC) were described more than 100 years ago by Ramon y Cajal. For many years these cells were identified only by non-specific histological stains and later, more reliably, by electron microscopy. Ultrastructural features and the anatomical locations of ICC suggested important physiological roles for these cells. A breakthrough occurred in our ability to study ICC when it was recognized that antibodies for Kit could be used to identify ICC, even in living tissues. Signalling via Kit, a receptor tyrosine kinase, is also necessary for ICC development and maintenance of phenotype. Thus, blocking Kit, by a variety of techniques, caused loss of ICC in experimental animals and demonstrated the critical physiological functions of these cells in gastrointestinal motility. Loss of ICC in human gastrointestinal diseases may contribute to the motor pathologies observed. Unrestrained Kit signalling leads to the transformation of ICC and the development of gastrointestinal stromal tumours. Now ICC-like cells have been identified in a variety of smooth muscle tissues, and the race is on to discover whether these cells have equivalent or even novel functions in organs outside the gastrointestinal tract. This perspectives article gives a short overview of the history of ICC research and directions for future investigation.