Disturbed balance between SOX2 and CDX2 in human vitelline duct anomalies and intestinal duplications

Congenital gastric-type heteroplasia is common in intestinal duplications and anomalies, which originate from incomplete resorption of the omphalomesenteric duct during development. Two transcription factors determine the proximodistal specification of the gastrointestinal tract, SOX2, expressed exclusively in the proximal part of the primitive gut, and CDX2, expressed solely in the distal part. Aberrant expression of these factors may result in abnormal development and congenital abnormalities. Therefore, we analyzed the expression of SOX2 and CDX2 in a number of pediatric intestinal anomalies. We investigated the expression pattern of SOX2 and CDX2 in three congenital intestinal anomalies in which ectopic gastric tissue may be present, Meckel's diverticulum (N = 8), persistent ductus omphalomesentericus (N = 14), and intestinal duplications (N = 8). CDX2, but not SOX2, was detected in intestinal epithelial cells in tissue lacking gastric heteroplasia. In gastric-type heteroplasia, a reciprocal expression pattern existed between SOX2 and CDX2 in the gastric and intestinal tissues, respectively. Interestingly, patches of CDX2-positive cells were present within the gastric mucosa in a subset of Meckel's diverticula and intestinal duplications, suggesting that it is not the absence of CDX2, but rather the ectopic expression of SOX2 that leads to gastric tissue in the prospective intestinal tissue. This is in concordance with our previous mouse studies. Collectively, our data indicate that a fine balance between SOX2 and CDX2 expression in the gastrointestinal tract is essential for proper development and that ectopic expression of SOX2 may lead to malformations of the gut.