Development of the enteric nervous system, smooth muscle and interstitial cells of Cajal in the human gastrointestinal tract

Abstract

The generation of functional neuromuscular activity within the pre-natal gastrointestinal tract requires the coordinated development of enteric neurons and glial cells, concentric layers of smooth muscle and interstitial cells of Cajal (ICC). We investigated the genesis of these different cell types in human embryonic and fetal gut material ranging from weeks 4-14. Neural crest cells (NCC), labelled with antibodies against the neurotrophin receptor p75NTR, entered the foregut at week 4, and migrated rostrocaudally to reach the terminal hindgut by week 7. Initially, these cells were loosely distributed throughout the gut mesenchyme but later coalesced to form ganglia along a rostrocaudal gradient of maturation; the myenteric plexus developed primarily in the foregut, then in the midgut, and finally in the hindgut. The submucosal plexus formed approximately 2-3 weeks after the myenteric plexus, arising from cells that migrated centripetally through the circular muscle layer from the myenteric region. Smooth muscle differentiation, as evidenced by the expression of alpha-smooth muscle actin, followed NCC colonization of the gut within a few weeks. Gut smooth muscle also matured in a rostrocaudal direction, with a large band of alpha-smooth muscle actin being present in the oesophagus at week 8 and in the hindgut by week 11. Circular muscle developed prior to longitudinal muscle in the intestine and colon. ICC emerged from the developing gut mesenchyme at week 9 to surround and closely appose the myenteric ganglia by week 11. By week 14, the intestine was invested with neural cells, longitudinal, circular and muscularis mucosae muscle layers, and an ICC network, giving the fetal gut a mature appearance.

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

“…Only 9.5 ± 3% of the cells were positive for squamous cell marker CK4, and a very small population of cells (4±2.5%), stained for p75NTR, which has been reported as an esophageal progenitor cell marker. 53,54 Immunoperoxidase staining of mAbDas-1 (Figure 1ai) showed weak diffuse staining of cytoplasm with increased staining on the periphery of the cells, which is more evident by immunofluorescence assay (Figure 1b). …”

“…52 We utilized the BAR-T cell line as a model to identify the specific cell phenotype in a heterogeneous 52 cell population that could demonstrate molecular and/or cell phenotypic changes following chronic exposure to acid and bile. We utilized specific cell-phenotype markers: CK8/18 for columnar, CK4 for squamous, mAbDas-1 for colonic phenotype and p75NTR suggested as marker for esophageal progenitors 53,54 and quantified the cells displaying each phenotype. We compared the expression of all of these markers sequentially in the BAR-T cells, following a single 5-min exposure (acute exposure) to acid (pH 4) or bile at pH 7.4, or bile at pH 4, and then continued similar exposure, every day, for up to 6 weeks (chronic exposure).…”

Gastroschisis in Mice Lacking Aortic Carboxypeptidase-Like Protein Is Associated With a Defect in Neuromuscular Development of the Eviscerated Intestine

“…SMC play a pivotal role in the intestinal peristalsis. It is known that the intestinal musculature develops sequentially beginning in the circular layer, followed by the longitudinal layer, and finally within the muscularis mucosa (19). We found a major difference in the extent of SMC development and maturation between controls and the EI.…”

Le système nerveux entérique et l’unité neuro-glio-épithéliale digestive

“…Cette colonisation représente la plus longue migration cellulaire durant le développement embryonnaire. Chez l'homme, elle dure environ trois semaines et le colon est colonisé à la fin de neuf semaines de gestation (Wallace & Burns, 2005). Les CCNs forment d'abord le plexus myentérique et, dans un second temps, donnent naissance au plexus sous-muqueux (provenant de CNN situées dans le plexus myentérique).…”