Development of interstitial cells of Cajal in the human digestive tract as the result of reciprocal induction of mesenchymal and neural crest cells

Abstract

Neural crest cells (NCC) can migrate into different parts of the body and express their strong inductive potential. In addition, they are multipotent and are able to differentiate into various cell types with diverse functions. In the primitive gut, NCC induce differentiation of muscular structures and interstitial cells of Cajal (ICC), and they themselves differentiate into the elements of the enteric nervous system (ENS), neurons and glial cells. ICC develop by way of mesenchymal cell differentiation in the outer parts of the primitive gut wall around the myenteric plexus (MP) ganglia, with the exception of colon, where they appear simultaneously also at the submucosal border of the circular muscular layer around the submucosal plexus (SMP) ganglia. However, in a complex process of reciprocal induction of NCC and local mesenchyma, c‐kit positive precursors are the first to differentiate, representing probably the common precursors of ICC and smooth muscle cells (SMC). C‐kit positive precursors could represent a key impact factor regarding the final differentiation of NCC into neurons and glial cells with neurons subsequently excreting stem cell factor (SCF) and other signalling molecules. Under the impact of SCF, a portion of c‐kit positive precursors lying immediately around the ganglia differentiate into ICC, while the rest differentiate into SMC.

Chronic idiopathic constipation in adults: epidemiology, pathophysiology, diagnosis and clinical management

“…The interstitial cells of Cajal act as a pacemaker, mediating between the signals of the enteric nervous system and intestinal smooth muscle. 18 Colonic contents can also move in a retrograde direction, which is more marked after a meal and potentially provides a "brake" to prevent rapid rectal filling. 19 At the same time, there is also a general postprandial increase in colonic motor activitythe socalled gastrocolic reflex.…”

“…Serotonin activates receptors, which send signals via the myenteric nerve plexus, propagating a wave of intestinal smooth muscle contraction and propelling luminal contents. The interstitial cells of Cajal act as a pacemaker, mediating between the signals of the enteric nervous system and intestinal smooth muscle 18 …”

The Telocytes: Ten Years after Their Introduction in the Scientific Literature. An Update on Their Morphology, Distribution, and Potential Roles in the Gut

“…Although ICCs originate from the mesenchyma, their strict relation with the neurons starts from the embryo period. Studies in human and animal [ 76 , 77 ] embryos show that in the primitive intestine, the development and differentiation of the mesenchymal cells in ICCs are under the control of the neural crest cells, but also that once the ICCs differentiate, they would stop the neural crest cells’ proliferation, favoring the differentiation in neurons. Interestingly, the expression of the c-Kit receptors on ICCs might constitute a key factor in this differentiative circuit.…”

Intestinal proinflammatory macrophages induce a phenotypic switch in interstitial cells of Cajal

“…The C-KIT ligand stem cell factor (SCF) in the intestine is mostly secreted by enteric neurons (22). Of the 1-, 2-, and 3-week old Ednrb -/mice, SCF expression was decreased in the distal colon, but was normally expressed in the middle and proximal colon as detected by western blotting (Supplemental Figure 4A-D, Figure 4B and C) and RT-PCR (Supplemental Figure 5A and B, Supplemental Figure 6B Figure 7A and B, Figure 4A).…”