W KIT GENE REQUIRED FOR INTERSTITIAL-CELLS OF CAJAL AND FOR INTESTINAL PACEMAKER ACTIVITY/

THE pacemaker activity in the mammalian gut is responsible for generat ing anally propagating phasic contractions, The cellular basis for thi s intrinsic activity is unknown. The smooth muscle cells of the extern al muscle layers and the innervated cellular network of interstitial c ells of Cajal, which is closely associated with the external muscle la yers of the mammalian gut, have both been proposed to stimulate pacema ker activity(1-5). The interstitial cells of Cajal were identified in the last century but their developmental origin and function have rema ined unclear. Here we show that the interstitial cells of Cajal expres s the Kit receptor tyrosine kinase. Furthermore, mice with mutations i n the dominant white spotting (W) locus, which have cellular defects i n haematopoiesis, melanogenesis and gametogenesis(6) as a result of mu tations in the Kit gene(7,8) also lack the network of intestitial cell s of Cajal associated with Auerbach's nerve plexus and intestinal pace maker activity.