Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control gastrulation movements in parallel to the Wnt/PCP pathway

Abstract

SUMMARYThe 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 pdgfr. 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.

Coco regulates dorsoventral specification of germ layers via inhibition of TGFβ signalling

“…Coco has been shown to inhibit the TGFβ ligands Xnr and Activin (Bell et al, 2003), factors that are essential for mesoderm and 4179 RESEARCH REPORT Germ layer specification endoderm specification (Thomsen et al, 1990;Green et al, 1992;Jones et al, 1993;Jones et al, 1995;Yasuo and Lemaire, 1999;Ninomiya et al, 1999;Kofron et al, 1999;Takahashi et al, 2000;Piepenburg et al, 2004;Luxardi et al, 2010). We propose that Coco is required in normal development to ensure correct specification of the germ layers by limiting TGFβ signals in the marginal zone to allow mesoderm specification, and inhibiting them in animal poles to allow ectoderm specification.…”

“…Vg1 is expressed vegetally before the onset of Nodal and Activin expression, and has been shown to promote these other TGFβ signals (Joseph and Melton, 1998). Nodal and Activin are required for both mesoderm and endoderm formation, with the highest activity level in endoderm and moderate levels in mesoderm (Hudson et al, 1997;Yasuo and Lemaire, 1999;Piepenburg et al, 2004;Kimelman, 2006;Shen, 2007;Luxardi et al, 2010).…”

Embryonic Stem Cells: Introducing Exogenous Regulators into Embryonic Stem Cells

“…Grouped cell movement and sequential spatio-temporal expressions of gene sets was observed after implantation. As a consequence of gastrulation, the embryos have three germ layers, endoderm, mesoderm and ectoderm (Hassoun et al, 2010;Luxardi et al, 2010). This process is accomplished with the forming of the axis (Rocha et al, 2010).…”

NODAL and SHH dose-dependent double inhibition promotes an HPE-like phenotype in chick embryos

“…The NODAL signaling pathway has been extensively studied during cleavage and blastula stages in zebrafish; NODAL acts in a dose-dependent and time-dependent manner during the mid-to-late blastula stage to specify most mesodermal and endodermal cell types (Hagos and Dougan, 2007;Gritsman et al, 2000). The total absence of NODAL is embryonically lethal, whereas a hypomorphic allele of Nodal or chemical inactivation results in anterior patterning defects including cyclopia in mice, zebrafish and Xenopus (Lowe et al, 2001;Vincent et al, 2003;Hagos and Dougan, 2007;Luxardi et al, 2010). These defects are strictly dependent on the degree of NODAL inactivation and on the embryonic stage.…”

“…These defects are strictly dependent on the degree of NODAL inactivation and on the embryonic stage. Consistent with the importance of this pathway during development, inactivation at early stages leads to very severe phenotypes, and the critical time-window of requirement for NODAL activity during forebrain formation is difficult to define (Shen, 2007;Luxardi et al, 2010).…”