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XB-ART-40945
Development 2010 Feb 01;1373:417-26. doi: 10.1242/dev.039735.
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Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control gastrulation movements in parallel to the Wnt/PCP pathway.

Luxardi G , Marchal L , Thomé V , Kodjabachian L .


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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.

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Species referenced: Xenopus
Genes referenced: dvl2 fn1 foxi1 foxl1 gsc has2 lefty1 nodal nodal1 nodal2 nodal5.4 nodal6 not pcdh8 pcdh8.2 pdgfra rnd1 sox17a sox2 tbxt wnt11 wnt11b
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