Reprogramming of intestinal differentiation and intercalary regeneration in Cdx2 mutant mice

摘要

The homeobox gene Cax2, a homologue of the Drosophile gene caudal, has been implicated in the control of cell differentiation in the intestinal epithelium. Recently, we showed that mice in which one allele of the Cdx2 gene had been inactivated by homologous recoinbination developed multiple intestinal polyp-like lesions that did not express Cdx2 and that contained areas of squamous metaplasia in the form of keratinizing stratified squamous epithelium, similar to that occurring in the mouse esophagus and forestomach. We have now examined colonic lesions from 98 Cdx2+/- mice and report that the lesions are composed of heterotopic stomach and small intestinal mucosa. We conclude that Cdx2 directs endodermal differentiation toward a caudal phenotype and that haploinsufFicient levels of expression in the developing distal intestine lead to homeotic transformation to a more rostral endodermal phenotype, such as forestomach epithe- lium that does not express Cdx2 during normal development. Intercalary growth (epimorphic regeneration), which previ- ously has never been described in mammals, then occurs, resulting in the ordered "filling in" of tissue types at the discontinuity between the gastric and colonic epithelia. This intercalary growth in a restricted space results in the forma- tion of the polypoid lesions observed.