Fig. 3
From: Different approaches for transformation of mesenchymal stem cells into hepatocyte-like cells
Molecular pathways in embryogenesis of the liver. Production of the liver parenchymal cells starts from the anterior part of the primary liver bud. FGF from cardiac mesoderm and BMP, which is mediated by SMAD4, interfere in hepatic induction through RAS/MAP kinase pathway and BMP signaling. GATA4 regulates expression of the secreted BMP4, which is highly expressed in the STM mesenchymal cells at the 8-somite stage. At early somite stages WNT signaling acts around 7–11 somites to repress the expression of Hhex. At around 21 somites, the matrix surrounding the basal surface of the epithelium is degraded, and E-cadherin expression is downregulated in the hepatic cells by the action of MMPs. GATA4 and/or GATA6 cause hepatoblast development by transactivating the Hhex promoter. Around 25 somites, Onecut-1 and Onecut-2 are redundantly essential for hepatoblast migration. Prox1 also promotes hepatoblast proliferation and migration from the primary liver bud. Tbx3 normally promotes a hepatocyte fate and represses a cholangiocyte fate through the expression of Hnf4a and c/EBPa. FGF fibroblast growth factor, HNF hepatocyte nuclear factor, BMP bone morphogenetic protein, Fox A Fork-head box protein A, Hhex hematopoietically expressed homeobox, STM septum transversum, MMPs matrix metalloproteinases, c/EBPa CCAAT-enhancer-binding proteins, Tbx3 T-Box 3, Prox1 prospero-related homeobox transcription factor