Distribution, development and proliferation of interstitial cells of Cajal in murine colon: an immunohistochemical study from neonatal to adult life

Abstract

This paper aimed at investigating the alterations in interstitial cells of Cajal (ICC) in the proximal, middle and distal colon of mice from 0-day to 56-day post-partum (P0-P56) by immunohistochemistry. The Kit(+) ICC, which situated around myenteric nerve plexus (ICC-MY) were prominent at birth, meanwhile those cells within the smooth muscle layers (ICC-IM) and in the connective tissue beneath serosa (ICC-SS) began to appear. ICC-SM, which located at the submucosal border of circular muscle layer emerged at P6 in the proximal colon and subsequently in the distal colon at P8, and ICC in the oral side of colon revealed an earlier development in morphology and a higher density than that in the anal side. The density of ICC altered obviously during postnatal period, and the estimated total amount of ICC increased approximately 30 folds at P56 than that at P0. Some Kit(+)/Ki67(+) and Kit(+)/BrdU(+) cells were observed in ICC-MY, ICC-IM and ICC-SS, but not in ICC-SM from P0 to P24. Our result indicates a proximal to distal and transmural gradient development of ICC in the postnatal colon along with a dramatic increase of ICC cell number from neonatal to adult life, and an age-dependent proliferation of ICC is also involved.

Regional Distribution of Interstitial Cells of Cajal (ICC) in Human Stomach

“…Therefore, the regional unique distribution of ICC seemed to be related to unique physiological function of each GI tract. In fact, the density of ICC in colon was much higher at proximal colon, where strong haustral contractions toward anus begin [30]. Recently, ICC was reported also in human stomach, small intestine and colon [15,31,32], and all subtypes of ICC were shown to develope as early as 4 th month development stage [4].…”

Late Embryonic and Postnatal Development of Interstitial Cells of Cajal in Mouse Esophagus: Distribution, Proliferation and Kit Dependence

“…A similarly organized ICC network has been observed in the canine distal esophagus [Berezin et al, 1994]. ICC in the esophagus are similar to those located within the muscular layers (ICC-IM) of the stomach, intestines and cecum [Serio et al, 1991;Burns et al, 1997;Horisawa et al, 1998;Ordog et al, 1999;Han et al, 2010a]. Previous studies have shown that ICC-IM play an important role in NO-dependent neurotransmission in the lower esophageal and pyloric sphincter, and loss of these cells may lead to dysfunction of relaxation and normal motility in the sphincters [Ward et al, 1998].…”

“…We have shown that the density of ICC in the murine colon and small intestine did not change considerably from birth to adulthood [Torihashi et al, 1997;Mei et al, 2009c;Han et al, 2010a]; however, in the esophagus, ICC density gradually decreased from E17.5 to adulthood (P36), and the value at P36 was about one twentieth of that observed at P0. Moreover, it should be noted that the ICC in the intestines gradually form an intact and complex network after birth, but the close connection between those cells in the esophagus could be found only from E17.5 to P7; thereafter, these cells were distributed separately along with a decrease in density.…”

“…Smooth muscle precursors are predominant in the muscle layers of the murine esophagus during the embryonic period [Patapoutian et al, 1995;Sang and Young, 1997], and striated muscle cells gradually appear and replace SMC before adulthood. Previous studies have indicated that ICC increased gradually within the small intestine and colon from the neonatal stage to adulthood, and the proliferation of ICC is involved in the postnatal development of gut [Mei et al, 2009c;Han et al, 2010a;Tharayil et al, 2010]. With respect to the dramatic changes observed in muscle cells, the postnatal development of ICC in the esophagus may differ from other segments of the GI tract, and is still not well understood yet.…”

“…Previous investigations have shown that ICC would continue to increase in cell number rather than to remain constant during the postnatal period in both small intestine and colon, and an age-dependent proliferation was involved along with the dramatic increase in intestinal diameter and length [Mei et al, 2009c;Han et al, 2010a]. In this case, we wanted to know whether or not proliferation is also involved in the postnatal development of ICC in the esophagus, since there is a similar increase in length and diameter.…”