TL;DR: It is concluded that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.
Abstract: The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.
TL;DR: It is reported that hepatocyte nuclear factor 4α (Hnf4α) is essential for morphological and functional differentiation of hepatocytes, accumulation of hepatic glycogen stores and generation of a hepatic epithelium, and the morphogenetic parameters controlled by Hnf 4α in hepatocytes are essential for normal liver architecture, including the organization of the sinusoidal endothelium.
Abstract: Although advances have been made in understanding cell differentiation, only rudimentary knowledge exists concerning how differentiated cells form tissues and organs. We studied liver organogenesis because the cell and tissue architecture of this organ is well defined. Approximately 60% of the adult liver consists of hepatocytes that are arranged as single-cell anastomosing plates extending from the portal region of the liver lobule toward the central vein. The basal surface of the hepatocytes is separated from adjacent sinusoidal endothelial cells by the space of Disse, where the exchange of substances between serum and hepatocytes takes place. The hepatocyte's apical surface forms bile canaliculi that transport bile to the hepatic ducts. Proper liver architecture is crucial for hepatic function and is commonly disrupted in disease states, including cirrhosis and hepatitis. Here we report that hepatocyte nuclear factor 4alpha (Hnf4alpha) is essential for morphological and functional differentiation of hepatocytes, accumulation of hepatic glycogen stores and generation of a hepatic epithelium. We show that Hnf4alpha is a dominant regulator of the epithelial phenotype because its ectopic expression in fibroblasts induces a mesenchymal-to-epithelial transition. Most importantly, the morphogenetic parameters controlled by Hnf4alpha in hepatocytes are essential for normal liver architecture, including the organization of the sinusoidal endothelium.
TL;DR: The data indicate that the in vitro ES differentiation system has a potential to generate mature hepatocytes and has also been found useful in analyzing the role of growth factors and intracellular signaling molecules in hepatic development.
TL;DR: A novel zebrafish transgenic line, the gutGFP line, is introduced that expresses GFP throughout the digestive system, and this tool is used to analyze the development of the liver, finding that in zebra fish, unlike what has been reported in mouse, endothelial cells do not appear to be necessary for the budding of this organ.
TL;DR: Advances in these areas include new genes and experimental models for studying liver development, the role of HNF6 and HNF1beta transcription factors and notch signaling in the hepatocyte-biliary cell lineage decision, the identification of genomic targets for HNF4, and H NF4's role in controlling hepatic epithelial structure and the sinusoidal organization of the liver.