Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors
F Clotman, P Jacquemin… - Genes & …, 2005 - genesdev.cshlp.org
Genes & development, 2005•genesdev.cshlp.org
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 …
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 …
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.
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