Control of liver cell fate decision by a gradient of TGF beta signaling modulated by Onecut transcription factors
(2005) Genes & Development — Vol. 19, n° 16, p. 1849-1854 (2005)
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- Abstract
- 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/TGFbeta signaling controls hepatoblast differentiation. High activin/TGFbeta signaling is required near the portal vein for differentiation of biliary cells. The Onecut transcription factors HNF-6 and OC-2 inhibit activin/TGFbeta signaling in the parenchyma, and this allows normal hepatocyte differentiation. In the absence of Onecut factors, the shape of the activin/TGFbeta gradient is perturbed and the hepatoblasts differentiate into hybrid cells that display characteristics of both hepatocytes and biliary cells. Thus, a gradient of activin/TGFbeta signaling modulated by Onecut factors is required to segregate the hepatocytic and the biliary lineages.
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Clotman, F., Courtoy, P., Jacquemin, P., Plumb-Rudewiez, N., Pierreux, C., Van Der Smissen, P., Dietz, H. C., Rousseau, G., & Lemaigre, F. (2005). Control of liver cell fate decision by a gradient of TGF beta signaling modulated by Onecut transcription factors. Genes & Development, 19(16), 1849-1854. https://doi.org/10.1101/gad.340305 (Original work published 2005)