W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity

JD Hulzinga, L Thuneberg, M Klüppel, J Malysz… - Nature, 1995 - nature.com
Nature, 1995nature.com
THE pacemaker activity in the mammalian gut is responsible for generating anally
propagating phasic contractions. The cellular basis for this intrinsic activity is unknown. The
smooth muscle cells of the external muscle layers and the innervated cellular network of
interstitial cells of Cajal, which is closely associated with the external muscle layers of the
mammalian gut, have both been proposed to stimulate pacemaker activity1–5. The
interstitial cells of Cajal were identified in the last century but their developmental origin and …
Abstract
THE pacemaker activity in the mammalian gut is responsible for generating anally propagating phasic contractions. The cellular basis for this intrinsic activity is unknown. The smooth muscle cells of the external muscle layers and the innervated cellular network of interstitial cells of Cajal, which is closely associated with the external muscle layers of the mammalian gut, have both been proposed to stimulate pacemaker activity1–5. The interstitial cells of Cajal were identified in the last century but their developmental origin and function have remained unclear. Here we show that the interstitial cells of Cajal express the Kit receptor tyrosine kinase. Furthermore, mice with mutations in the dominant white spotting (W) locus, which have cellular defects in haematopoiesis, melanogenesis and gametogenesis6 as a result of mutations in the Kit gene7,8, also lack the network of intestitial cells of Cajal associated with Auerbach's nerve plexus and intestinal pacemaker activity.
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