Evolution of the Role of RA and FGF Signals in the Control of Somitogenesis in Chordates.

Thomas Brand,Stéphanie Bertrand,Angel R De Lera,Daniel Aldea,Lucie Subirana,Silvan Oulion,Ildiko Somorjai,Hector Escriva

doi:10.1371/journal.pone.0136587

Thomas Brand, Stéphanie Bertrand + Show 6 more

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https://doi.org/10.1371/journal.pone.0136587

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Abstract

During vertebrate development, the paraxial mesoderm becomes segmented, forming somites that will give rise to dermis, axial skeleton and skeletal muscles. Although recently challenged, the "clock and wavefront" model for somitogenesis explains how interactions between several cell-cell communication pathways, including the FGF, RA, Wnt and Notch signals, control the formation of these bilateral symmetric blocks. In the cephalochordate amphioxus, which belongs to the chordate phylum together with tunicates and vertebrates, the dorsal paraxial mesendoderm also periodically forms somites, although this process is asymmetric and extends along the whole body. It has been previously shown that the formation of the most anterior somites in amphioxus is dependent upon FGF signalling. However, the signals controlling somitogenesis during posterior elongation in amphioxus are still unknown. Here we show that, contrary to vertebrates, RA and FGF signals act independently during posterior elongation and that they are not mandatory for posterior somites to form. Moreover, we show that RA is not able to buffer the left/right asymmetry machinery that is controlled through the asymmetric expression of Nodal pathway actors. Our results give new insights into the evolution of the somitogenesis process in chordates. They suggest that RA and FGF pathways have acquired specific functions in the control of somitogenesis in vertebrates. We propose that the "clock and wavefront" system was selected specifically in vertebrates in parallel to the development of more complex somite-derived structures but that it was not required for somitogenesis in the ancestor of chordates.

Highlights

Segmentation along the antero-posterior body axis is a morphological feature found in several metazoan lineages
The region without somites is comparable to what is observed in embryos in which only Fibroblast Growth Factor (FGF) signalling is inhibited as highlighted by Myosin Light Chain-alkali (MLC) expression (Fig 1J, 1K and 1M)
Our data suggest that the anterior border of Hox1 expression does not define the limit between somites that depend upon FGF signalling for their formation and somites whose formation is not controlled by FGF

Summary

Introduction

Segmentation along the antero-posterior body axis is a morphological feature found in several metazoan lineages. An elegant paradigm was first proposed by Cooke and Zeeman in 1976 to explain the regular formation of segments during somitogenesis termed the "clock and wavefront" model [3] Molecular evidence for this hypothesis came more than twenty years later and our understanding of how somitogenesis is controlled in vertebrates has been highly improved since [4, 5]. Our current understanding of the "clock and wavefront" model relies on the specific interactions of several signalling pathways, including the retinoic acid (RA), the Fibroblast Growth Factor (FGF), the Wnt (Wingless/INT-1) and the Notch pathways. These interactions permit the synchronized activation of segmentation genes in the PSM in response to the "segmentation clock" [5]. As a consequence of the interaction between the clock and the wavefront, the cells of the PSM that pass the determination border during one oscillation of the clock define a pre-patterned somite [5]

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