The zebrafish onecut gene hnf-6 functions in an evolutionarily conserved genetic pathway that regulates vertebrate biliary development
The zebrafish onecut gene hnf-6 functions in an evolutionarily conserved genetic pathway that regulates vertebrate biliary development
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DOI：
10.1016/j.ydbio.2004.06.016
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发表时间：
2004-10-15
影响因子：
2.7
通讯作者：
Pack, M
中科院分区：
文献类型：
--
作者：
Matthews, RP;Lorent, K;Pack, M
靶向破坏onecut转录因子hnf-6改变哺乳动物胆道系统发育。我们已经确定了一个相关的斑马鱼cDNA表达在发育中的肝脏，是一个功能性的哺乳动物hnf-6的直系同源物。斑马鱼hnf-6反义基因敲减干扰肝内胆管系统发育。斑马鱼hnf-6的敲低改变了vhnf 1和其他哺乳动物基因的表达。共注射编码斑马鱼vhnf 1的mRNA拯救hnf-6吗啡肽的胆汁表型。这些实验有力地表明hnf-6和vhnf 1在一个进化上保守的调节胆道发育的途径中发挥作用。hnf-6或vhnf 1的强制表达也产生胆汁表型。在功能丧失和获得实验中胆管发育的改变表明斑马鱼胆管细胞对hnf-6介导的基因转录剂量敏感。(C)2004年爱思唯尔公司All rights reserved.
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. (C) 2004 Elsevier Inc. All rights reserved.