Kit/stem cell factor receptor-induced phosphatidylinositol 3′-kinase signalling is not required for normal development and function of interstitial cells of Cajal in mouse gastrointestinal tract

Signalling mediated by the receptor tyrosine kinase c-Kit is required for normal development of interstitial cells of Cajal (ICC). c-Kit activates several signalling pathways, including the phosphatidylinositol 3′-kinase (PI3′-kinase) pathway. The signals required for ICC development and maintenance are not well understood. Studies indicate a role for PI3′-kinase. We studied ICC function and morphology in mice homozygous for the tyrosine 719 to phenylalanine c-Kit mutation, which disrupts all PI3′-kinase binding to c-Kit. Functionally, the electrical slow waves in the jejunum and inhibitory junction potentials were normal in adult mutants. Morphologically, the distribution of ICC was not altered in mutants. There was no difference in the density of ICC in the jejunum of adults or newborns from quantitative analysis of c-Kit immunoreactivity. The number of ICC obtained in culture was the same using mutants or wild-type littermates. The density and organization of nerves in the jejunum of mutants was not affected. Deletion of c-Kit-induced PI3′-kinase signalling does not affect the function or development of ICC in the mouse. This is an important and counterintuitive result, given the role of PI3′-kinase signalling down-stream of c-kit and the role of both c-Kit and PI3′-kinase individually in ICC development.