The zebrafish onecut gene hnf-6 functions in an evolutionarily conserved genetic pathway that regulates vertebrate biliary development

• Published in: Developmental biology 2004-10, Vol.274 (2), p.245-259
• Main Authors: Matthews, Randolph P., Lorent, Kristin, Russo, Pierre, Pack, Michael
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Bile Ducts - embryology; Bile Ducts - ultrastructure; Biliary development; Biological Evolution; Danio rerio; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Freshwater; Gene Expression Regulation, Developmental; Hepatocyte Nuclear Factor 1-beta; Hepatocyte Nuclear Factor 6; hnf-6; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; In Situ Hybridization; Lipids - secretion; Liver - embryology; Liver - metabolism; Liver - physiology; Liver - ultrastructure; Molecular Sequence Data; Oligonucleotides, Antisense - genetics; Oligonucleotides, Antisense - metabolism; Pancreas - cytology; Pancreas - embryology; Pancreas - metabolism; RNA, Messenger - metabolism; Sequence Alignment; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Zebrafish; Zebrafish - anatomy & histology; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - physiology; Zebrafish Proteins
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2004.06.016

Targeted disruption of the onecut transcription factor, hnf-6, alters mammalian biliary system development. We have identified a related zebrafish cDNA expressed in the developing liver that is a functional ortholog of mammalian hnf-6. Antisense-mediated knockdown of zebrafish hnf-6 perturbs development of the intrahepatic biliary system. Knockdown of zebrafish hnf-6 alters expression of vhnf1 and the zebrafish orthologs of other mammalian genes regulated by hnf-6. Coinjection of mRNA encoding zebrafish vhnf1 rescues the biliary phenotype of hnf-6 morphants. These experiments strongly suggest that hnf-6 and vhnf1 function within an evolutionarily conserved pathway that regulates biliary development. Forced expression of either hnf-6 or vhnf1 also produces biliary phenotypes. Altered bile duct development in both loss- and gain-of-function experiments suggests that zebrafish biliary cells are sensitive to the dosage of hnf-6-mediated gene transcription.