|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.
|Source:||Developmental Biology 274(2): 245-259 (Journal)|
|Registered Authors:||Lorent, Kristin, Matthews, Randy, Pack, Michael|
|Keywords:||Biliary development; Zebrafish; hnf-6|
|PubMed:||15385156 Full text @ Dev. Biol.|
Matthews, R.P., Lorent, K., Russo, P., and Pack, M. (2004) The zebrafish onecut gene hnf-6 functions in an evolutionarily conserved genetic pathway that regulates vertebrate biliary development. Developmental Biology. 274(2):245-259.
ABSTRACTTargeted 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.