Figure 1.

Specification of the hepatic and pancreatic organ domains. (A) Sagittal view of a mouse embryo at E8.5. The endoderm (light beige) receives inductive signals from neighboring mesodermal tissues (septum transversum mesenchyme, cardiac mesoderm, somites, notochord). Consequently, hepatic (orange) and ventral pancreatic (green) organ domains form in the ventral foregut endoderm and a dorsal pancreatic (green) progenitor domain in the dorsal foregut. (B) Schematics of the factors controlling fate specification of the dorsal pancreatic endoderm. Activin and FGF2 secreted by the notochord repress expression of Sonic hedgehog (Shh) in the presumptive dorsal pancreatic endoderm, which in turn allows Pdx1 expression (Hebrok 2003). Pdx1 expression is further promoted by retinoic acid from the somites (Gittes 2009). (C) Schematic overview of the factors controlling the fate specification of hepatic and ventral pancreatic endoderm. Fibroblast growth factors (FGFs) secreted from the cardiac mesoderm and bone morphogenetic proteins (BMPs) produced by the septum transversum mesenchyme promote hepatic fate in the anterior ventral foregut, while suppressing ventral pancreatic identity (Zaret 2016). In the posterior ventral foregut, extrinsic signaling cues, such as Wnt5a (Rodríguez-Seguel et al. 2013), and cell-intrinsic transcriptional regulators, such as Tgif2 (Cerdá-Esteban et al. 2017), establish ventral pancreatic identity while suppressing hepatic fate. Subsequently, specified organ domains turn on hepatic (Albumin) or pancreatic marker genes (Pdx1). Slit ligands from the overlying mesenchyme bind to Robo2 receptors expressed in the ventral pancreatic endoderm and facilitate the maintenance of pancreatic identity (Escot et al. 2018).