Les facteurs de transcription Sox contrôlent le développement des canaux biliaires
(2011)
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- Authors
- Supervisors
- Lemaigre, Frédéric
- Abstract
- Liver tissue predominantly consists of hepatocytes, which carry out metabolic functions and are responsible for bile production, and biliary cells or cholangiocytes, which line biliary ducts through which bile flows to the digestive tract. These two cell populations originate from common precursors called hepatoblasts. In mice, hepatocyte and biliary lineages segregate at embryonic stage E13. This process is controlled by a network of transcription factors. Biliary cells differentiate around branches of the portal vein and constitute a ring of cells, the ductal plate, where biliary duct formation is initiated. In order to characterize the transcriptional control network involved in biliary duct development, we have first identified new markers of biliary development, namely SOX9 and osteopontin. Using these new markers, we were able to uncover that biliary duct development occurs via an undescribed mode of tubulogenesis, duringwhich transient, primitive ductal structures are formed from the ductal plate. These transient structures are asymmetrical, that is they are lined by biliary cells on their portal side while they are lined by hepatoblasts on their parenchymal side. Maturation of these structures takes place by differentiation of hepatoblasts toward biliary cells, resulting in a radial symmetry of the biliary ducts which become entirely lined by cholangiocytes. In addition, we have revealed an early expression of two members of the transcription factor family Sry-related HMG box (SOX), namely SOX4 and SOX9, in biliary cells. The role of both genes was investigated by means of an in vivo knockout approach. This showed that SOX4 and SOX9 stimulate biliary duct morphogenesis and differentiation. In conclusion, our observations lead to a better understanding of the morphogenesis and of the transcriptional mechanisms which control the differentiation of hepatoblasts into biliary cells Our work offeris new perspectives for diagnosis and understanding human biliary duct malformations
- Affiliations
Citations
Antoniou, A. (2011). Les facteurs de transcription Sox contrôlent le développement des canaux biliaires. https://hdl.handle.net/2078.5/111947