Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Bile Ducts / embryology
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Bile Ducts / ultrastructure
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Biological Evolution*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Developmental
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Hepatocyte Nuclear Factor 1-beta
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Hepatocyte Nuclear Factor 6
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism*
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Humans
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In Situ Hybridization
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Lipid Metabolism
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Liver / embryology*
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Liver / metabolism
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Liver / physiology
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Liver / ultrastructure
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Molecular Sequence Data
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Oligonucleotides, Antisense / genetics
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Oligonucleotides, Antisense / metabolism
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Pancreas / cytology
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Pancreas / embryology
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Pancreas / metabolism
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RNA, Messenger / metabolism
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Sequence Alignment
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Trans-Activators / genetics*
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Zebrafish / anatomy & histology
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Zebrafish / embryology*
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Zebrafish / genetics
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Zebrafish / physiology
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Zebrafish Proteins
Substances
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DNA-Binding Proteins
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HNF1B protein, human
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Hepatocyte Nuclear Factor 6
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Homeodomain Proteins
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Oligonucleotides, Antisense
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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Zebrafish Proteins
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hnf1ba protein, zebrafish
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Hepatocyte Nuclear Factor 1-beta