TY - JOUR
T1 - Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors
AU - Clotman, Frédéric
AU - Jacquemin, Patrick
AU - Plumb-Rudewiez, Nicolas
AU - Pierreux, Christophe E.
AU - Van Der Smissen, Patrick
AU - Dietz, Harry C.
AU - Courtoy, Pierre J.
AU - Rousseau, Guy G.
AU - Lemaigre, Frédéric P.
PY - 2005/8/15
Y1 - 2005/8/15
N2 - During liver development, hepatocytes and biliary cells differentiate from common progenitors called hepatoblasts. The factors that control hepatoblast fate decision are unknown. Here we report that a gradient of activin/TGFβ signaling controls hepatoblast differentiation. High activin/TGFβ signaling is required near the portal vein for differentiation of biliary cells. The Onecut transcription factors HNF-6 and OC-2 inhibit activin/TGFβ signaling in the parenchyma, and this allows normal hepatocyte differentiation. In the absence of Onecut factors, the shape of the activin/TGFβ gradient is perturbed and the hepatoblasts differentiate into hybrid cells that display characteristics of both hepatocytes and biliary cells. Thus, a gradient of activin/TGFβ signaling modulated by Onecut factors is required to segregate the hepatocytic and the biliary lineages.
AB - During liver development, hepatocytes and biliary cells differentiate from common progenitors called hepatoblasts. The factors that control hepatoblast fate decision are unknown. Here we report that a gradient of activin/TGFβ signaling controls hepatoblast differentiation. High activin/TGFβ signaling is required near the portal vein for differentiation of biliary cells. The Onecut transcription factors HNF-6 and OC-2 inhibit activin/TGFβ signaling in the parenchyma, and this allows normal hepatocyte differentiation. In the absence of Onecut factors, the shape of the activin/TGFβ gradient is perturbed and the hepatoblasts differentiate into hybrid cells that display characteristics of both hepatocytes and biliary cells. Thus, a gradient of activin/TGFβ signaling modulated by Onecut factors is required to segregate the hepatocytic and the biliary lineages.
KW - Activin/TGFβ signaling gradient
KW - Hepatic differentiation
KW - Hepatoblasts
KW - Liver development
KW - Onecut transcription factors
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U2 - 10.1101/gad.340305
DO - 10.1101/gad.340305
M3 - Article
C2 - 16103213
AN - SCOPUS:23944458649
VL - 19
SP - 1849
EP - 1854
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 16
ER -