Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves.
OBJECTIVE
Development of interstitial cells of Cajal (ICC) requires signaling via Kit receptors. Kit is activated by stem cell factor (SCF), but the source of SCF in the bowel wall is unclear and controversy exists about whether enteric neurons express the SCF required for ICC development.


METHODS
Glial cell line-derived neurotrophic factor (GDNF) knockout mice, which lack enteric neurons throughout most of the gut, were used to determine whether neurons are necessary for ICC development. ICC distributions were determined with Kit immunofluorescence, and function of ICC was determined by intracellular electrical recording.


RESULTS
ICC were normally distributed throughout the gastrointestinal tracts of GDNF-/- mice. Intracellular recordings from aganglionic gastrointestinal muscles showed normal slow wave activity at birth in the stomach and small intestine. Slow waves developed normally in aganglionic segments of small bowel placed into organ culture at birth. Quantitative polymerase chain reaction showed similar expression of SCF in the muscles of animals with and without enteric neurons. Expression of SCF was demonstrated in isolated intestinal smooth muscle cells.


CONCLUSIONS
These data suggest that enteric neurons are not required for the development of functional ICC. The circular smooth muscle layer, which develops before ICC, may be the source of SCF required for ICC development.
Ward
S M
SM
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA. SEAN@physio.unr.edu
Ordög
T
T
Bayguinov
J R
JR
Horowitz
B
B
Epperson
A
A
Shen
L
L
Westphal
H
H
Sanders
K M
KM
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D004594:Electrophysiology; D017615:Enteric Nervous System / Q000166:cytology* / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology* / Q000294:innervation / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000166:cytology* / Q000294:innervation / Q000378:metabolism; D018377:Neurotransmitter Agents; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000096:biosynthesis*; D013270:Stomach / Q000166:cytology* / Q000294:innervation
D008024:Ligands; D018377:Neurotransmitter Agents; D019089:Stem Cell Factor; D012313:RNA; D019009:Proto-Oncogene Proteins c-kit