Endodermal and mesenchymal cross talk: a crossroad for the maturation of foregut organs

The developmental stages of each foregut organ are intimately linked to the development of the other foregut organs such that the ultimate function of any one foregut organ, such as the metabolic function of the liver, depends on organizational changes associated with the maturation of multiple foregut organs. These changes include: (i) proliferation of the intrahepatic bile ducts and hepatoblasts within the liver coinciding with parenchymal expansion, (ii) elongation of extrahepatic bile ducts, which allows for proper gallbladder (GB) formation, and (iii) duodenal elongation and rotation, which coincides with all of the above to connect the intrahepatic, extrahepatic, and pancreatic ductal systems with the intestine. It is well established that cross talk between endodermal and mesenchymal components of the foregut occurs, particularly regarding the vascularization of developing organs. Furthermore, genetic mutations in mesenchymal and hepatic compartments of the developing foregut result in similar foregut pathologies: hypoplastic liver, absence of GB, biliary atresia (intrahepatic and/or extrahepatic), and failure of gut elongation and rotation. Finally, these shared pathologies can be linked to deficiencies in genes specific to the septum transversum mesenchyme (Hes1, Hlx, and Foxf1) or liver (Hhex and Hnf6), illustrating the complexity of such cross talk.