Intestinal morphogenesis

Abstract

The molecular basis of endoderm differentiation and interaction with mesoderm to generate the mature intestine has been the focus of intensive investigation. Signaling pathways relevant to organogenesis may be recapitulated during oncogenesis. This review highlights recent studies of endoderm specification, differentiation and formation of the gut tube, the ontogeny of regional differentiation along the anterior-posterior and crypt-villus axes, and mechanisms of epithelial differentiation and epithelial-mesenchymal interactions during gut morphogenesis. Model organisms include zebrafish, Xenopus, Drosophila and the mouse. Fibroblast growth factors play critical roles in early endoderm differentiation and anterior-posterior patterning, and retinoids regulate left-right asymmetry and gut looping/rotation. Embryoid bodies derived from embryonic stem cells recapitulate many aspects of gut epithelial morphogenesis. Novel regulators of epithelial cell differentiation and epithelial-mesenchymal interactions have been identified (e.g. Mtgr1), and several known genes modulate these processes (e.g. PPARbeta/delta, Ptk6, GATA4). The role of Bmp, Hh and wnt signaling in morphogenesis continues to be elucidated. The complex process of intestinal morphogenesis involves interactions among multiple signaling pathways. Studies of morphogenesis are critical for elucidating the molecular basis of congenital gut defects and provide novel insight into intestinal oncogenic processes.