Abstract
Gut mesodermal tissues originate from the splanchnopleural mesenchyme. However, the embryonic gastrointestinal coelomic epithelium gives rise to mesenchymal cells, whose significance and fate are little known. Our aim was to investigate the contribution of coelomic epithelium-derived cells to the intestinal development. We have used the transgenic mouse model mWt1/IRES/GFP-Cre (Wt1cre) crossed with the Rosa26R-EYFP reporter mouse. In the gastrointestinal duct Wt1, the Wilms’ tumor suppressor gene, is specific and dynamically expressed in the coelomic epithelium. In the embryos obtained from the crossbreeding, the Wt1-expressing cell lineage produces the yellow fluorescent protein (YFP) allowing for colocalization with differentiation markers through confocal microscopy and flow cytometry. Wt1cre-YFP cells were very abundant throughout the intestine during midgestation, declining in neonates. Wt1cre-YFP cells were also transiently observed within the mucosa, being apparently released into the intestinal lumen. YFP was detected in cells contributing to intestinal vascularization (endothelium, pericytes and smooth muscle), visceral musculature (circular, longitudinal and submucosal) as well as in Cajal and Cajal-like interstitial cells. Wt1cre-YFP mesenchymal cells expressed FGF9, a critical growth factor for intestinal development, as well as PDGFRα, mainly within developing villi. Thus, a cell population derived from the coelomic epithelium incorporates to the gut mesenchyme and contribute to a variety of intestinal tissues, probably playing also a signaling role. Our results support the origin of interstitial cells of Cajal and visceral circular muscle from a common progenitor expressing anoctamin-1 and SMCα-actin. Coelomic-derived cells contribute to the differentiation of at least a part of the interstitial cells of Cajal.
Highlights
Intestinal motility disorders include a collection of pathologic processes secondary to alterations in the intestinal wall
Cells of the Wt1 Lineage are Already Abundant Since the Earliest Stages of Intestinal Development Wt1 protein expression is present in the coelomic epithelium and mesenchymal cells of the intestine by E10 (Fig. 1A–D), weakly in the fore and hindgut and stronger in the midgut (Fig. 1C)
Wt1 expression becomes uniformly observed throughout all the intestinal coelomic epithelium by E10.5 (Fig. 1E–F) when Wt1cre-yellow fluorescent protein (YFP) mesenchymal cells are already abundant, especially in the foregut and anterior midgut (Fig. 1H, I)
Summary
Intestinal motility disorders include a collection of pathologic processes secondary to alterations in the intestinal wall. These alterations may be congenital or secondary to degenerative changes due to systemic illness. Familial visceral myopathy is characterized by alterations in the smooth muscle fibers of the muscular layers of the intestinal wall causing a clinical picture of chronic intestinal pseudoobstruction. Some of these pathologies have been correlated with alterations in the network of interstitial cells of Cajal (ICC) [1]. Despite the potential importance of congenital factors in the pathogeny of these anomalies, the knowledge on the embryonic development of the mesodermal cell populations that contribute to the different intestinal tissues is still insufficient
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