We have engaged in a number of studies in our laboratory that have focused on the molecular mechanisms underlying gut formation, with particular attention being paid to the establishment of regional differences found in the entire gut and within each digestive organ. We have found from our analyses that the presumptive fate of the endoderm in the embryos of vertebrates is determined quite early during development, but the realization of this fate often requires molecular cues from the neighboring tissues such as the lateral plate mesoderm and the mesenchyme derived from it. The mesenchyme seems often to exert instructive or supportive induction effects and, in some cases, a completely inhibitory role during the differentiation of the endodermal epithelium. In addition, many reports on the formation of the stomach, intestine, liver and salivary gland in vertebrates, and of Drosophila gut, all indicate that the morphogenesis and cytodifferentiation of these organs are regulated by the regulated expression of genes encoding growth factors and transcription factors. We have further shown that the epithelium can regulate the differentiation of the mesenchyme into the connective tissue and the smooth muscle layers, thus demonstrating the occurrence of literally interactive processes in the development of the digestive organs.