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RESEARCH COMMUNICATION
signaling modulated by Onecut transcription factors
1 Hormone and Metabolic Research Unit, 2 Cell Biology Unit, Institute of Cellular Pathology and Université catholique de Louvain, 1200 Brussels, Belgium; 3 Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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/TGF
signaling controls hepatoblast differentiation. High activin/TGF signaling is required near the portal vein for differentiation of biliary cells. The Onecut transcription factors HNF-6 and OC-2 inhibit activin/TGF signaling in the parenchyma, and this allows normal hepatocyte differentiation. In the absence of Onecut factors, the shape of the activin/TGF gradient is perturbed and the hepatoblasts differentiate into hybrid cells that display characteristics of both hepatocytes and biliary cells. Thus, a gradient of activin/TGF signaling modulated by Onecut factors is required to segregate the hepatocytic and the biliary lineages.
[Keywords: Hepatoblasts; hepatic differentiation; activin/TGF signaling gradient; Onecut transcription factors; liver development]
Received February 14, 2005; revised version accepted June 14, 2005.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.340305.
E-MAIL lemaigre{at}horm.ucl.ac.be; FAX 32-2-764-75-07.
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