ZFIN ID: ZDB-PUB-041004-5
The zebrafish onecut gene hnf-6 functions in an evolutionarily conserved genetic pathway that regulates vertebrate biliary development
Matthews, R.P., Lorent, K., Russo, P., and Pack, M.
Date: 2004
Source: Developmental Biology   274(2): 245-259 (Journal)
Registered Authors: Lorent, Kristin, Matthews, Randy, Pack, Michael
Keywords: Biliary development; Zebrafish; hnf-6
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Bile Ducts/embryology
  • Bile Ducts/ultrastructure
  • Biological Evolution*
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Gene Expression Regulation, Developmental
  • Hepatocyte Nuclear Factor 1-beta
  • Hepatocyte Nuclear Factor 6
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism*
  • Humans
  • In Situ Hybridization
  • Lipids
  • 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/anatomy & histology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Zebrafish Proteins
PubMed: 15385156 Full text @ Dev. Biol.
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.