The homeobox gene Cdx2, a homologue of the Drosophila 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 recombination 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 epithelium that does not express Cdx2 during normal development. Intercalary growth (epimorphic regeneration), which previously 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 formation of the polypoid lesions observed.

Item Type:	Refereed Article
Research Division:	Biomedical and Clinical Sciences
Research Group:	Clinical sciences
Research Field:	Gastroenterology and hepatology
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Playford, RJ (Professor Ray Playford)
ID Code:	72876
Year Published:	1999
Web of Science® Times Cited:	241
Deposited By:	Research Division
Deposited On:	2011-09-02
Last Modified:	2011-09-05
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