Special Focus Research Article
Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract
Article first published online: 25 AUG 2006
Copyright © 2006 Wiley-Liss, Inc.
Volume 236, Issue 1, pages 60–72, January 2007
How to Cite
Beckett, E. A. H., Ro, S., Bayguinov, Y., Sanders, K. M. and Ward, S. M. (2007), Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract. Dev. Dyn., 236: 60–72. doi: 10.1002/dvdy.20929
- Issue published online: 19 DEC 2006
- Article first published online: 25 AUG 2006
- Manuscript Accepted: 1 JUL 2006
- National Institutes of Health. Grant Number: DK 41315
- gastrointestinal motility;
- imatinib mesylate;
- smooth muscle;
Interstitial cells of Cajal (ICC) are specialized cells in smooth muscle organs that generate and propagate pacemaker activity, receive inputs from motor neurons, and serve as mechanosensors. In the gastrointestinal tract, development and maintenance of the ICC phenotype have been linked to intracellular signaling via Kit, but its role in development of ICC during embryogenesis is controversial. Here we have studied the development of functional ICC-MY during the late gestational period in mice. Blocking Kit with a neutralizing antibody before and after development of spontaneous electrical activity (E17 to P0) caused loss of ICC-MY networks and pacemaker activity. ICC-MY and pacemaker activity developed normally in W/+ and WV/+ heterozygotes, but failed to develop between E17 to P0 in W/WV embryos with compromised Kit function. Muscles treated with Kit neutralizing antibody or the tyrosine kinase inhibitor, imatinib mesylate (STI571), from E17-P0 for 3 days caused loss of functionally developed ICC-MY networks, but ICC-MY and pacemaker activity recovered within 9 days after discontinuing treatment with neutralizing antibody or imatinib mesylate. These data suggest that Kit signaling is an important factor in lineage decision and in the development of functional ICC in late gestation. ICC-MY demonstrate significant plasticity in gastrointestinal tissues. Manipulation of the ICC phenotype might provide useful therapies in gastrointestinal disease where the Kit-positive cell population is either lost or amplified. Developmental Dynamics, 2006. © 2006 Wiley-Liss, Inc.