W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity.
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 activity. 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 gametogenesis as a result of mutations in the Kit gene, also lack the network of interstitial cells of Cajal associated with Auerbach's nerve plexus and intestinal pacemaker activity.
Huizinga
J D
JD
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Thuneberg
L
L
Klüppel
M
M
Malysz
J
J
Mikkelsen
H B
HB
Bernstein
A
A
D000200:Action Potentials; D000818:Animals; D003238:Connective Tissue / Q000648:ultrastructure; D005260:Female; D007421:Intestine, Small / Q000294:innervation / Q000502:physiology* / Q000648:ultrastructure; D008751:Methylene Blue; D051379:Mice; D009130:Muscle, Smooth / Q000502:physiology; D009154:Mutation; D009197:Myenteric Plexus / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology; D010528:Peristalsis / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D008751:Methylene Blue