Ober Elke A, Verkade Heather, Field Holly A, Stainier Didier Y R
Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, and the Liver Center, University of California, San Francisco, 1550 Fourth Street, San Francisco, California 94143, USA.
Nature. 2006 Aug 10;442(7103):688-91. doi: 10.1038/nature04888. Epub 2006 Jun 21.
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, 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.
肺、肝脏和胰腺等内胚层器官沿着原始肠管在精确的位置形成。尽管有几种信号通路与肝脏形成有关，但到目前为止，尚未鉴定出专门调节肝脏特化的单一基因。在斑马鱼中，受精后22小时，肝脏特化的开始以hhex和prox1在内胚层的局部表达为标志。在这里，我们通过筛选影响内胚层器官形态发生的突变来鉴定一种独特的表型：普罗米修斯（prt）突变体在肝脏特化方面表现出严重但短暂的缺陷。定位克隆显示prt编码一种以前未鉴定的Wnt2b同源物。prt/wnt2bb在紧邻形成肝脏的内胚层的侧板中胚层的受限双侧区域表达。镶嵌分析表明侧板中胚层需要Prt/Wnt2bb，这与Wnt信号的诱导特性一致。综上所述，这些数据揭示了Wnt信号在肝脏特化中意想不到的积极作用，并表明沿肠管内胚层器官局部形成可能存在共同的机制。
