Journal
DEVELOPMENTAL BIOLOGY
Volume 404, Issue 2, Pages 136-148Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2015.05.012
Keywords
SOX transcription factors; Liver development; Biliary tract; Transcriptional network
Categories
Funding
- Interuniversity Attraction Pole Programme (Belgian Science Policy) [PVII-47]
- D.G. Higher Education and Scientific Research of the French Community of Belgium [ARC 10/15-029]
- Commission of the European Communities [238821]
- Alphonse and Jean Forton Fund
- Universite Catholique de Louvain
- F.R.S.-FNRS (Belgium) [3.4536.1, J.0058.15]
- Televie
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In developing liver, cholangiocytes derive from the hepatoblasts and organize to form the bile ducts. Earlier work has shown that the SRY-related High Mobility Group box transcription factor 9 (SOX9) is transiently required for bile duct development, raising the question of the potential involvement of other SOX family members in biliary morphogenesis. Here we identify SOX4 as a new regulator of cholangiocyte development. Liver-specific inactivation of SOX4, combined or not with inactivation of SOX9, affects cholangiocyte differentiation, apico-basal polarity and bile duct formation. Both factors cooperate to control the expression of mediators of the Transforming Growth Factor-beta, Notch, and Hippo-Yap signaling pathways, which are required for normal development of the bile ducts. In addition, SOX4 and SOX9 control formation of primary cilia, which are known signaling regulators. The two factors also stimulate secretion of laminin alpha 5, an extracellular matrix component promoting bile duct maturation. We conclude that SOX4 is a new regulator of liver development and that it exerts a pleiotropic control on bile duct development in cooperation with SOX9. (C) 2015 Elsevier Inc. All rights reserved.
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