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 +8 more
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TLDR
A gradient of activin/TGFbeta signaling modulated by Onecut factors is required to segregate the hepatocytic and the biliary lineages.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.read more
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References
More filters
Journal ArticleDOI
How cells read TGF-beta signals.
TL;DR: The TGF-β family of cytokines can trigger a bewildering diversity of responses, depending on the genetic makeup and environment of the target cell.
Journal ArticleDOI
Making sense of latent TGFβ activation
TL;DR: This work considers the latent TGFβ complex as an extracellular sensor in which the TGF β propeptide functions as the detector, latent-TGFβ-binding protein (LTBP) functions as a localizer, and TGF-β functions as an effector.
Journal ArticleDOI
Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome
Enid Neptune,Pamela A. Frischmeyer,Dan E. Arking,Loretha Myers,Tracie E. Bunton,Barbara Gayraud,Francesco Ramirez,Lynn Y. Sakai,Harry C. Dietz +8 more
TL;DR: It is shown that mice deficient in fibrillin-1 have marked dysregulation of transforming growth factor-β (TGF-β) activation and signaling, resulting in apoptosis in the developing lung, and that perturbation of this function can contribute to the pathogenesis of disease.
Journal ArticleDOI
Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1
Linheng Li,Ian D. Krantz,Yu Deng,Yu Deng,Anna Genin,Amy B. Banta,Colin Collins,Ming Qi,Barbara J. Trask,Wen Lin Kuo,Joanne Cochran,Teresa Costa,Mary Ella M Pierpont,Elizabeth B. Rand,David A. Piccoli,Leroy Hood,Nancy B. Spinner +16 more
TL;DR: Four distinct coding mutations in JAG1 are demonstrated, providing evidence that it is the causal gene for Alagille syndrome, and supporting the hypothesis that haploinsufficiency for this gene is one of the mechanisms causing the Alagile syndrome phenotype.
Journal ArticleDOI
Mutations in the human Jagged1 gene are responsible for Alagille syndrome
Takaya Oda,Abdel G. Elkahloun,Brian L. Pike,Kazuki Okajima,Ian D. Krantz,Anna Genin,David A. Piccoli,Paul S. Meltzer,Nancy B. Spinner,Francis S. Collins,Settara C. Chandrasekharappa +10 more
TL;DR: It is concluded that AGS is caused by haploinsufficiency of JAG1, the human homologue of rat Jagged1, which encodes a ligand for the Notch receptor, an attractive candidate gene for a developmental disorder in humans.