Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors

Frédéric Clotman, Patrick Jacquemin, Nicolas Plumb-Rudewiez, Christophe E. Pierreux, Patrick Van Der Smissen, Harry C. Dietz, Pierre J. Courtoy, Guy G. Rousseau, Frédéric P. Lemaigre

Research output: Contribution to journalArticle

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/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.

Original languageEnglish (US)
Pages (from-to)1849-1854
Number of pages6
JournalGenes and Development
Volume19
Issue number16
DOIs
StatePublished - Aug 15 2005

Keywords

  • Activin/TGFβ signaling gradient
  • Hepatic differentiation
  • Hepatoblasts
  • Liver development
  • Onecut transcription factors

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors'. Together they form a unique fingerprint.

  • Cite this

    Clotman, F., Jacquemin, P., Plumb-Rudewiez, N., Pierreux, C. E., Van Der Smissen, P., Dietz, H. C., Courtoy, P. J., Rousseau, G. G., & Lemaigre, F. P. (2005). Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors. Genes and Development, 19(16), 1849-1854. https://doi.org/10.1101/gad.340305