Cytodifferentiation of the Interstitial Cells of Cajal of Mouse Colonic Circular Muscle Layer

Abstract

Cytodifferentiation of the interstitial cells of Cajal related to the plexus entericus extremus and located on the inner face of the circular muscle layer of the mouse colon was studied in fetuses at term, unfed neonates, suckling and weaning young animals. In fetuses at term, the interstitial cells of Cajal are not found and their precursor cells are not identifiable among the cells present in the submucosal area facing the circular muscle layer, i.e., undifferentiated cells (mainly close to nerve fibers) and fibroblast-like cells (contacting each other and the developing smooth-muscle cells). Cells putatively considered as precursors of interstitial cells of Cajal, fibroblast-like cells rich in mitochondria, are present in unfed neonates (in small numbers) and in suckling animals (in large numbers). Differentiating interstitial cells of Cajal are undoubtedly recognizable during the second week of postnatal life (suckling period). Some of them have mixed fibroblastic- and interstitial-cell features and some have many interstitial-cell features. Both these cell types are already in contact with each other and differentiating and differentiated smooth-muscle cells. The undifferentiated cells, still present in unfed neonates, envelop the nerve fibers and differentiate as Schwann cells during the suckling period. During this period, as the nerve endings of the plexus entericus extremus develop, they immediately contact the differentiating interstitial cells of Cajal. During the weaning period, these cells are quite well differentiated although they do not have the same morphology as in adult animals before 30 days of age. Concomitantly, the nerve endings of the plexus entericus extremus contain an increasing number of synaptic vesicles.

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

“…Scale bar a = 50 m, refers to all panels Distribution alterations of ICC During embryonic period, ICC progenitors begin to express Kit protein, a special marker of ICC, in the foregut on embryonic day 12 (E12) and hindgut of mouse on E14, respectively (Torihashi et al 1995;Faussone-Pellegrini et al 1996;Torihashi et al 1997;Ward et al 1997;Wu et al 2000), and then these cells gather at the outer border of the circular muscle layer in the proximal colon at E15 and gradually form an ICC-MY-like cellular network at E19 and further develop into mature ICC-MY after birth . ICC-SM are not detected by either immunohistochemistry or EM before birth, and only putative ICC precursors, Wbroblast-like cells rich in mitochondria, are observed under EM (Faussone-Pellegrini 1987;Ward et al 1997). Our results show that the Kit positive cells are prominent between the smooth muscle layers around myenteric nerve plexus (ICC-MY) at birth, and a small number of ICC can be seen within adjecent smooth muscle layers (ICC-IM) and beneath serosa (ICC-SS).…”

“…ICC-SM cannot be detected in murine colon by either immunohistochemistry or under electron microscope (EM) before birth, and these cells appear about 1 week after birth (Faussone-Pellegrini 1987;Ward et al 1997;Vanderwinden et al 2000). However, the postnatal development of ICC in murine colon, from neonatal to adult life, is of little concern, in spite of the fact that the absence and underdevelopment of ICC are strongly suggested to contribute to a number of colonic motility disorders, in neonates, infants or adults, such as Hirschsprung's disease (Vanderwinden et al 1996), pseudo-obstruction (Kenny et al 1998), isolated hypoganglionosis (Rolle et al 2002) and slow transit constipation (Wedel et al 2002).…”

Roles of stem cell factor on the depletion of interstitial cells of Cajal in the colon of diabetic mice

“…Transmission electron microscopy was performed in colonic tissues to identify the changes of ICC (6). Tissues were processed according to a standard procedure.…”

Interstitial cells of Cajal in human gut and gastrointestinal disease

“…In human small intestine, ICC-AP have a myoïd ultrastructure (Faussone-Pellegrini, 1987b;FaussonePellegrini and Cortesini, 1983;Rumessen, 1994;Rumessen et al, 1993;Thuneberg, 1991, 1996;Torihashi et al, 1999): dense bodies and dense bands are frequent, but more irregularly distributed than in SMC. Large bundles of intermediate (10 nm) filaments and a well-developed sER are characteristic.…”

“…If the appearance of ICC changes significantly under pathological conditions, these cells may not be recognized as ICC. The same holds true for early developmental stages, when ICC precursors do not yet exhibit the characteristic features of mature ICC and thus may elude recognition as ICC (Faussone-Pellegrini, 1987b). (2) The lack of detectable Kit-ir may indicate either the absence of ICC or may also indicate the loss of Kit-ir by ICC.…”