Epithelial-mesenchymal interactions are necessary for the normal development of various digestive organs. In chicken proventriculus (glandular stomach), morphogenesis and differentiation of the epithelium depend upon the inductive signals coming from underlying

The digestive organs comprise the endodermal epithelium and mesenchyme derived from the splanchnic mesoderm. For morphogenesis and cytodifferentiation of these organs, epithelial-mesenchymal interactions are essential (Le Douarin, 1975; Wessels, 1977; Haffen et al., 1987; Yasugi and Mizuno, 1990; Yasugi, 1993). We have been studying the mechanisms of differentiation of the proventricular epithelial cells using experimental and molecular approaches. The proventriculus is a glandular stomach situated anterior to the gizzard (muscular stomach) and is characterized by the development of compound glands (Romanoff, 1960). Morphogenesis of the proventricular glands starts around day 6.5 of incubation. Groups of epithelial cells invaginate into the underlying mesenchyme to form the gland structures. These cells then express the embryonic chicken pepsinogen (ECPg) gene, a differentiation marker of the glandular epithelial cells, from day 9 of incubation (Hayashi et al., 1988). In contrast, non-invaginating epithelial cells express the chicken spasmolytic polypeptide (cSP) gene, encoding a mucus-related protein, and differentiate into luminal cells (Tabata and Yasugi, 1998). Expressions of ECPg and cSP are almost completely exclusive (Tabata and Yasugi, 1998). Previous studies have reported that the formation of the glands depends upon induction from the underlying mesenchyme and competence of the epithelium to this inductive signal. The epithelia of the esophagus, proventriculus and gizzard can form glands under the influence of the proventricular mesenchyme, while intestinal epithelium never responds to the same influence (Takiguchi et al., 1986; Urase et al., 1996), indicating that the competence is restricted to epithelia of anterior digestive organs (Yasugi and Mizuno, 1990). Results of tissue recombination experiments using lung mesenchyme suggest that molecules identical or similar to the proventricular mesenchymal factors also exist in lung mesenchyme (Urase et al., 1996). Conversely the mesenchymal cells of the gizzard, situated posterior to the proventriculus, inhibit the differentiation of associated epithelium into glands (Urase and Yasugi, 1993). These results suggest the existence in the mesenchyme of proventriculus or gizzard of specific factors involved in the differentiation of the epithelium. We have further confirmed that proventricular mesenchymal factors are soluble (Koike and Yasugi, 1999), although the exact molecular nature of the mesenchymal factors is still unknown. 981 Development 127, 981-988 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV3026