The Nodal Inhibitor Coco Is a Critical Target of Leftward Flow in Xenopus
The Nodal Inhibitor Coco Is a Critical Target of Leftward Flow in Xenopus
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DOI：
10.1016/j.cub.2010.02.061
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发表时间：
2010-04-27
期刊：
影响因子：
9.2
通讯作者：
Blum, Martin
中科院分区：
文献类型：
--
作者：
Schweickert, Axel;Vick, Philipp;Blum, Martin
脊椎动物的侧侧性，表现为器官[1]的不对称放置，依赖于左侧外侧板中皮层[2]的节点信号级联的不对称激活。在鱼类、两栖动物和哺乳动物中，由纤毛驱动的细胞外液向左流动作用于节点级联的上游[3-6]。流动的直接目标仍然难以捉摸。在非洲爪蟾中，流动发生在胚胎背中线的胃冷顶板（GAP）[4,7]。GAP由第二个双边对称的节点表达域[8]包围。在这里，我们确定节点抑制剂Coco是流动的关键目标。Coco和Xenopus node相关1 （Xnr1）在近侧纤毛GAP细胞中共表达。Coco在GAP的左侧被下调，作为流量的直接读数。血流的消融阻止了Coco的抑制，而Xnrl的表达与血流无关。通过敲除左侧的Coco来挽救流诱导的侧性缺陷。在GRP细胞中，Coco和Xnr1的平行敲低恢复了血流受损胚胎的偏侧性缺陷，表明Coco通过gap表达的Xnr1起作用。因此，可可作为一个关键的流动目标，表明对称性被流动介导的中线节点抑制的左不对称释放打破。
Vertebrate laterality, which is manifested by asymmetrically placed organs [1], depends on asymmetric activation of the Nodal signaling cascade in the left lateral plate mesoderm [2]. In fish, amphibians, and mammals, a cilia-driven leftward flow of extracellular fluid acts upstream of the Nodal cascade [3-6]. The direct target of flow has remained elusive. In Xenopus, flow occurs at the gastrocoel roof plate (GAP) in the dorsal midline of the embryo [4, 7]. The GAP is bordered by a second, bilaterally symmetrical Nodal expression domain [8]. Here we identify the Nodal inhibitor Coco as a critical target of flow. Coco and Xenopus Nodal-related 1 (Xnr1) are coexpressed in the lateralmost ciliated GAP cells. Coco becomes downregulated on the left side of the GAP as a direct readout of flow. Ablation of flow prevented Coco repression, whereas Xnrl expression was independent of flow. Loss of flow-induced laterality defects were rescued by knockdown of Coco on the left side. Parallel knockdown of Coco and Xnrl in GRP cells restored laterality defects in flow-impaired embryos, demonstrating that Coco acted through GAP-expressed Xnr1. Coco thus acts as a critical target of flow, suggesting that symmetry is broken by flow-mediated left-asymmetric release of Nodal repression at the midline.