Lefty acts as an essential modulator of Nodal activity during sea urchin oral-aboral axis formation
Lefty acts as an essential modulator of Nodal activity during sea urchin oral-aboral axis formation
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DOI：
10.1016/j.ydbio.2008.04.012
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发表时间：
2008-08-01
影响因子：
2.7
通讯作者：
Lepage, Thierry
中科院分区：
文献类型：
--
作者：
Duboc, Veronique;Lapraz, Francois;Lepage, Thierry
Nodal在海胆胚胎口-口轴形成过程中起着关键作用。在口腔组织中心早期表达，需要通过驱动口-口基因调控网络来指定口腔和体外外胚层领土。已经提出了一种依赖于Nodal的自激活和远程拮抗剂Lefty的扩散的口-口轴规范模型，该模型导致了口场内Nodal活性的急剧限制。本文描述了左旋基因的表达模式，并分析了其在二次轴形成过程中的作用。左侧表达开始于淋巴结后的128细胞阶段，迅速局限于口腔外胚层，然后在原肠胚形成后向右侧转移。与先前的工作一致，在Lefty过表达的胚胎中，无论是口外胚层还是体外外胚层都没有被指定。相反，当Lefty的功能被阻断时，大部分外胚层通过异位表达nodal转化为口腔外胚层。在限制区域内重新引入lefty mRNA导致了节点表达的剂量依赖效应。值得注意的是，在lefty缺失胚胎的8细胞期将lefty mRNA注射到一个卵裂球中可以阻断整个外胚层的淋巴结表达，这与lefty在其他模型中的高度扩散特性一致。综上所述，这些结果表明Lefty对于口-口轴的形成至关重要，并表明Lefty在海胆胚胎中作为节点信号的远程抑制剂。(C) 2008爱思唯尔公司版权所有。
Nodal is a key player in the process regulating oral-aboral axis formation in the sea urchin embryo. Expressed early within an oral organizing centre, it is required to specify both the oral and aboral ectoderm territories by driving an oral-aboral gene regulatory network. A model for oral-aboral axis specification has been proposed relying on the self activation of Nodal and the diffusion of the long-range antagonist Lefty resulting in a sharp restriction of Nodal activity within the oral field. Here, we describe the expression pattern of lefty and analyse its function in the process of secondary axis formation. lefty expression starts at the 128-cell stage immediately after that of nodal, is rapidly restricted to the presumptive oral ectoderm then shifted toward the right side after gastrulation. Consistently with previous work, neither the oral nor the aboral ectoderm are specified in embryos in which Lefty is overexpressed. Conversely, when Lefty's function is blocked, most of the ectoderm is converted into oral ectoderm through ectopic expression of nodal. Reintroducing lefty mRNA in a restricted territory of Lefty depleted embryos caused a dose-dependent effect on nodal expression. Remarkably, injection of lefty mRNA into one blastomere at the 8-cell stage in Lefty depleted embryos blocked nodal expression in the whole ectoderm consistent with the highly diffusible character of Lefty in other models. Taken together, these results demonstrate that Lefty is essential for oral-aboral axis formation and suggest that Lefty acts as a long-range inhibitor of Nodal signalling in the sea urchin embryo. (C) 2008 Elsevier Inc. All rights reserved.