Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts.
Dev Biol
; 404(2): 136-48, 2015 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-26033091
ABSTRACT
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-ß, 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 α5, 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.
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Base de dados:
MEDLINE
Assunto principal:
Ductos Biliares Intra-Hepáticos
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Fatores de Transcrição SOXC
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Fatores de Transcrição SOX9
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article