Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm

Mesodermal signaling is critical for patterning the embryonic endoderm into different tissue domains. Classical tissue transplant experiments in the c hick and recent studies in the mouse indicated that interactions with the c ardiogenic mesoderm are necessary and sufficient to induce the liver in the ventral foregut endoderm. Using molecular markers and functional assays, w e now show that septum transversum mesenchyme cells, a distinct mesoderm ce ll type, are closely apposed to the ventral endoderm and contribute to hepa tic induction. Specifically, using a mouse Bmp4 null mutation and an inhibi tor of BMPs, we find that BMP signaling from the septum transversum mesench yme is necessary to induce liver genes in the endoderm and to exclude a pan creatic fate. BMPs apparently function, in part, by affecting the levels of the GATA4 transcription factor, and work in parallel to FGF signaling from the cardiac mesoderm. BMP signaling also appears critical for morphogeneti c growth of the hepatic endoderm into a liver bud. Thus, the endodermal dom ain for the liver is specified by simultaneous signaling from distinct meso dermal sources.