Institut de Biologie du Développement de Marseille Luminy, UMR 6216, CNRS-Université de la Méditerranée, Case 907, 13288 Marseille Cedex 09, France.
Development. 2010 Feb;137(3):417-26. doi: 10.1242/dev.039735. Epub 2010 Jan 7.
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 pdgfralpha. 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.
脊椎动物的体节模式是通过两个主要步骤建立的。首先，中胚层诱导将前内胚层、中胚层和外胚层祖细胞分离出来。其次，这些祖细胞在原肠胚形成过程中通过许多复杂的运动进行空间重排，形成一个包含三个同心胚层的胚胎，并沿着背腹、前后和左右轴极化。虽然人们对中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，Nodal 信号对于诱导中胚层是必需的，这使得对其在后期原肠胚形成过程中的潜在作用的分析变得困难。通过时间依赖性抑制，我们表明在 Xenopus 中，Nodal 信号在中胚层诱导和原肠胚形成运动中发挥连续作用。Nodal 活性对于轴向中胚层的会聚延伸和头部中胚层的迁移是必需的。通过使用 morpholino 介导的敲低，我们发现 Nodal 配体 Xnr5 和 Xnr6 一起对于中胚层诱导是必需的，而 Xnr1 和 Xnr2 则在后期控制原肠胚形成运动。这种控制是通过对关键运动效应基因的直接调节来实现的，例如 papc、has2 和 pdgfralpha。有趣的是，然而，Nodal 似乎不会动员已知控制细胞和组织极性的 Wnt/PCP 途径。这项研究为分析脊椎动物原肠胚形成过程中 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，说明了基因家族在进化中扩张导致的亚功能化。
