Interstitial cells of Cajal (ICC) are important regulatory cells in the smo
oth muscle coats of the digestive tract. Expression of the Kit receptor tyr
osine kinase was used in this study as a marker to study their distribution
and development in the striated musculature of the mouse esophagus. Sectio
ns and whole-mounts were studied by immunohistochemistry. Kit(w-lacZ) trans
genic mice, which carry the lacZ reporter gene inserted in place of the fir
st exon of the Kit gene, were processed for Xgal histochemistry, for quanti
tative analysis and for ultrastructural studies. Spindle-shaped ICC were sc
arce in both muscle layers of the thoracic esophagus, while their number in
creased steeply toward the cardia in the striated portion of the intraabdom
inal esophagus. They did not form networks and had no relationship with int
rinsic myenteric ganglia and motor end-plates. They were often close to ner
ve fibers immunoreactive for neuronal nitric oxide synthase (nNOS), vasoact
ive intestinal polypeptide (VIP) or neuropeptide Y (NPY), but not to fibers
immunoreactive for substance P (SP), calcitonin gene related peptide (CGRP
), enkephalin, or the capsaicin receptor VR1. They were present in the fetu
s but absent in adult ICC-deficient Kit(W-lacZ)/Kit(Wv) mice. Interstitial
cells of Cajal were identified by electron microscopy by their ultrastructu
re in the striated muscle of the esophagus and exhibited Xgal labeling, whi
le fibroblasts and muscle cells were unlabeled. Interstitial cells of Cajal
are scattered between striated muscle cells in the mouse esophagus. They a
re close to nerves with defined neurochemical coding and could possibly rep
resent specialized esophageal spindle proprioceptors.