Mesodermal Wnt2b signalling positively regulates liver specification
Mesodermal Wnt2b signalling positively regulates liver specification
复制标题
DOI：
10.1038/nature04888
复制
发表时间：
2006-08-10
期刊：
影响因子：
64.8
通讯作者：
Stainier, Didier Y. R.
中科院分区：
文献类型：
--
作者：
Ober, Elke A.;Verkade, Heather;Stainier, Didier Y. R.
内胚层器官如肺、肝和胰腺出现在沿着原肠管的精确位置。虽然有几种信号通路与肝脏形成有关（1，2），但迄今为止还没有发现单一基因专门调节肝脏特化。在斑马鱼中，肝脏特化的开始是由受精后22小时hhex和hx 1的局部内胚层表达标记的。在这里，我们使用了一个影响内胚层器官形态发生的突变筛选，以确定一个独特的表型：普罗米修斯（prt）突变体表现出深刻的，虽然短暂的，在肝脏特化缺陷。定位克隆显示，prt编码一个以前未确定的Wnt 2b同源。PRT/WNT 2BB在直接邻近肝形成内胚层的侧板中胚层的限制性双侧区域中表达。镶嵌分析表明，要求Prt/Wnt 2bb在侧板中胚层，Wnt信号的诱导特性一致。综上所述，这些数据揭示了Wnt信号传导在肝脏特化中的意想不到的积极作用，并表明了内胚层器官沿着肠管局部形成的可能共同主题。
Endodermal organs such as the lung, liver and pancreas emerge at precise locations along the primitive gut tube. Although several signalling pathways have been implicated in liver formation(1,2), so far no single gene has been identified that exclusively regulates liver specification. In zebrafish, the onset of liver specification is marked by the localized endodermal expression of hhex and prox1 at 22 hours post fertilization. Here we used a screen for mutations affecting endodermal organ morphogenesis to identify a unique phenotype: prometheus ( prt) mutants exhibit profound, though transient, defects in liver specification. Positional cloning reveals that prt encodes a previously unidentified Wnt2b homologue. prt/ wnt2bb is expressed in restricted bilateral domains in the lateral plate mesoderm directly adjacent to the liver- forming endoderm. Mosaic analyses show the requirement for Prt/ Wnt2bb in the lateral plate mesoderm, in agreement with the inductive properties of Wnt signalling. Taken together, these data reveal an unexpected positive role for Wnt signalling in liver specification, and indicate a possible common theme for the localized formation of endodermal organs along the gut tube.