1. Liver development
The biliary tract is constituted by intrahepatic bile ducts which collect the bile produced by the hepatocytes, and by extrahepatic ducts which drain the bile from the liver to the intestine. Biliary cells, also called cholangiocytes, delineate the lumen of the bile ducts and modify the composition of the bile. These cells, like hepatocytes, derive from liver progenitor cells called hepatoblasts. We investigate how those biliary cells differentiate from hepatoblasts and how they contribute to set up the bile ducts.
Our discovery of the Onecut transcription factors Onecut-1 (OC-1/HNF-6), OC-2 and OC-3, and the subsequent phenotypic characterization of HNF-6 and OC-2 knockout mice lead to the identification of transcriptional and signaling networks regulating bile duct development. We also found that biliary development proceeds according to a unique process characterized by transient asymmetry. Current efforts are devoted to the characterization of the transcription factors, microRNAs and signal transduction pathways that control bile duct development . Our preferred model organism to investigate bile duct development is the mouse, and this includes generation and analysis of transgenic mouse lines.
In collaboration with clinical centers, we investigate how the knowledge gained from our fundamental studies can be translated in the understanding of the pathophysiology of human biliary diseases. The latter include ductal plate malformations as well as polycystic diseases.
Development of bile ducts. Left panel: In embryos, hepatoblasts (grey) differentiate to ductal plate cholangiocytes (green) which form a ring of cells around the branches of the portal vein (blue). Middle panel: hepatoblasts become apposed to the ductal plate cells and delineate a developing duct. The latter is asymmetrical as it is lined on the portal side by cholangiocytes (dark green) and on the parenchymal side by hepatoblasts. Right panel: when the ducts have matured, they are entirely lined by cholangiocytes, while parenchymal hepatoblasts have differentiated to hepatocytes (brown) which line up as cords (from Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev. Cell, 18, 175-189, 2010).
During liver development, hepatocytes differentiate from hepatoblasts and progressively mature to acquire their metabolic functions. We have shown that Onecut transcription factors play an essential role in hepatocyte maturation. We currently investigate how Onecut and other transcription factors control this process.
Our research is performed with national and foreign collaborating groups. These collaborations include our participation to the Belgian Science Policy-sponsored Interuniversity Attraction Pole (IUAP/PAI) network and to the European-Union-funded network BOLD .
To know more... (pdf chapter of the last de Duve Institute report)
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