Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control gastrulation movements in parallel to the Wnt/PCP pathway
Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control gastrulation movements in parallel to the Wnt/PCP pathway
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DOI：
10.1242/dev.039735
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发表时间：
2010-02-01
期刊：
影响因子：
4.6
通讯作者：
Kodjabachian, Laurent
中科院分区：
文献类型：
--
作者：
Luxardi, Guillaume;Marchal, Leslie;Kodjabachian, Laurent
脊椎动物的身体计划是建立在两个主要步骤。首先，中内胚层诱导挑选出潜在的内胚层、中胚层和外胚层祖细胞。其次，这些祖细胞在原肠胚形成期间通过许多复杂的运动进行空间重排，以产生包含三个同心胚层的胚胎，沿着背腹，前后和左右轴极化。虽然对中内胚层诱导的分子机制了解很多，但控制原肠胚形成运动的信号才刚刚开始被揭示。在脊椎动物中，需要Nodal信号来诱导中内胚层，这排除了在原肠胚形成的后期过程中对其潜在作用的分析。使用时间依赖性抑制，我们表明，在非洲爪蟾，Nodal信号在中内胚层诱导和原肠胚运动中起着顺序的作用。节的活动是必要的收敛延伸轴中胚层和头部中胚层迁移。使用吗啉代介导的敲除，我们发现，Nodal配体Xnr 5和Xnr 6共同需要中内胚层诱导，而Xnr 1和Xnr 2的行动后，控制原肠胚运动。这种控制是通过直接调节关键的运动效应基因，如papc，has 2和pdgf α。然而，有趣的是，Nodal似乎并没有动员Wnt/PCP途径，这是已知的控制细胞和组织极性。这项研究为分析脊椎动物原肠胚形成期间由Nodal信号控制的遗传程序和细胞行为开辟了道路。它还提供了一个很好的例子，说明基因家族在进化中扩展而导致的亚功能化。
The vertebrate body plan is established in two major steps. First, mesendoderm induction singles out prospective endoderm, mesoderm and ectoderm progenitors. Second, these progenitors are spatially rearranged during gastrulation through numerous and complex movements to give rise to an embryo comprising three concentric germ layers, polarised along dorsoventral, anteroposterior and left-right axes. Although much is known about the molecular mechanisms of mesendoderm induction, signals controlling gastrulation movements are only starting to be revealed. In vertebrates, Nodal signalling is required to induce the mesendoderm, which has precluded an analysis of its potential role during the later process of gastrulation. Using time-dependent inhibition, we show that in Xenopus, Nodal signalling plays sequential roles in mesendoderm induction and gastrulation movements. Nodal activity is necessary for convergent extension in axial mesoderm and for head mesoderm migration. Using morpholino-mediated knockdown, we found that the Nodal ligands Xnr5 and Xnr6 are together required for mesendoderm induction, whereas Xnr1 and Xnr2 act later to control gastrulation movements. This control is operated via the direct regulation of key movement-effector genes, such as papc, has2 and pdgf alpha.. Interestingly, however, Nodal does not appear to mobilise the Wnt/PCP pathway, which is known to control cell and tissue polarity. This study opens the way to the analysis of the genetic programme and cell behaviours that are controlled by Nodal signalling during vertebrate gastrulation. It also provides a good example of the sub-functionalisation that results from the expansion of gene families in evolution.