Zebrafish Sox7 and Sox18 function together to control arterial-venous identity
Zebrafish Sox7 and Sox18 function together to control arterial-venous identity
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DOI：
10.1016/j.ydbio.2008.01.028
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发表时间：
2008-05-15
影响因子：
2.7
通讯作者：
Voz, Marianne L.
中科院分区：
文献类型：
--
作者：
Pendeville, Helene;Winandy, Marie;Voz, Marianne L.
Sox 7和Sox 18是Sox转录因子家族的F亚组成员，主要表达于内皮细胞。在人类中，Sox 18中的显性突变是以血管缺陷为特征的严重低血压-水肿-毛细血管扩张症病症的根本原因。然而，很少有人知道Sox 7和Sox 18在体内调节血管生成过程。我们克隆了Sox 7和Sox 18在斑马鱼中的同源基因，分析了它们的表达模式并进行了功能分析。这两个基因在体节发生期间在侧板中胚层中表达。在晚期，Sox 18在所有轴向血管中表达，而Sox 7表达主要限于背主动脉。单独敲除Sox 7或Sox 18不能揭示任何表型。相比之下，同时阻断这两个基因导致胚胎显示近端主动脉和动静脉分流的畸形，所有这些都可以解释在躯干和尾部观察到的循环缺乏。用一般内皮标记物对双morphants进行的基因表达分析显示，Sox 7和Sox 18是主要干血管的初始规格和定位的标志。然而，变形显示静脉Flt 4标记物在背主动脉中的异位表达以及伴随的动脉特异性标记物EphrinB 2a和Gridlock的减少。Sox 7/Sox 18 morphants和Gridlock突变体的表型之间的惊人相似性强烈表明Sox 7和Sox 18通过调节Gridlock表达来控制动脉-静脉身份。(C)2008年爱思唯尔公司All rights reserved.
Sox7 and Sox18 are members of the F-subgroup of Sox transcription factors family and are mostly expressed in endothelial compartments. In humans, dominant mutations in Sox 18 are the underlying cause of the severe hypotrichosis-lymphedema-telangiectasia disorder characterized by vascular defects. However little is known about which vasculogenic processes Sox7 and Sox18 regulate in vivo. We cloned the orthologs of Sox7 and Sox18 in zebrafish, analysed their expression pattern and performed functional analyses. Both genes are expressed in the lateral plate mesoderm during somitogenesis. At later stages, Sox18 is expressed in all axial vessels whereas Sox7 expression is mainly restricted to the dorsal aorta. Knockdown of Sox7 or Sox18 alone failed to reveal any phenotype. In contrast, blocking the two genes simultaneously led to embryos displaying dysmorphogenesis of the proximal aorta and arteriovenous shunts, all of which can account for the lack of circulation observed in the trunk and tail. Gene expression analyses performed with general endothelial markers on double morphants revealed that Sox7 and Sox18 are dispensable for the initial specification and positioning of the major trunk vessels. However, morphants display ectopic expression of the venous Flt4 marker in the dorsal aorta and a concomitant reduction of the artery-specific markers EphrinB2a and Gridlock. The striking similarities between the phenotype of Sox7/Sox18 morphants and Gridlock mutants strongly suggest that Sox7 and Sox18 control arterial-venous identity by regulating Gridlock expression. (C) 2008 Elsevier Inc. All rights reserved.