Retinoic acid coordinates somitogenesis and left–right patterning in vertebrate embryos

Abstract

A striking feature of the body plan of a majority of animals is bilateral symmetry. Almost nothing is known about the mechanisms controlling the symmetrical arrangement of the left and right body sides during development. Here we report that blocking the production of retinoic acid (RA) in chicken embryos leads to a desynchronization of somite formation between the two embryonic sides, demonstrated by a shortened left segmented region. This defect is linked to a loss of coordination of the segmentation clock oscillations1. The lateralization of this defect led us to investigate the relation between somitogenesis and the left–right asymmetry machinery2,3 in RA-deficient embryos. Reversal of the situs in chick4,5 or mouse6 embryos lacking RA results in a reversal of the somitogenesis laterality defect. Our data indicate that RA is important in buffering the lateralizing influence of the left–right machinery, thus permitting synchronization of the development of the two embryonic sides.

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Figure 1: Disulphiram blocks RA production and alters left–right coordination of the segmentation clock.
Figure 2: Asymmetry of somitogenesis in disulphiram-treated embryos.
Figure 3: Inversion of the situs leads to an inversion of the somitic defect in embryos lacking RA signalling.
Figure 4: Inversion of somitogenesis asymmetry in Raldh2-/-iv-/- mouse mutants showing situs inversion.

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Acknowledgements

We thank P. Chambon for his interest in this work; P. Dollé for discussions and for providing the Raldh2 mice; H. Hamada for providing the iv genotyping protocol; members of the Pourquié laboratory for sharing reagents and helpful discussions, especially T. Iimura for sharing his expertise with chick culture; B. Brede and P. Malapert for help with mouse genotyping; S. Esteban for artwork; and members of the Conaway and Workman laboratories, particularly J. Conaway and A. Paoletti for help with RP-HPLC, and J. Chen (on leave from University of Missouri – Kansas City) for help with the statistics. J.V. was supported by the Fondation pour la Recherche Médicale and by a Travelling Fellowship from the Company of Biologists and is on leave from IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France. Present work is supported by the Stowers Institute for Medical Research and by a grant from the NIH.

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Correspondence to Olivier Pourquié.

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Supplementary information

Supplementary Figure S1

Standard curve obtained by RP-HPLC after injection of different amounts of synthetic RA. Vertical bars represent the standard deviation. (JPG 103 kb)

Supplementary Figure S2

RA treatment rescues the somitogenesis asymmetry of disulphiram-treated embryos. (JPG 349 kb)

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Vermot, J., Pourquié, O. Retinoic acid coordinates somitogenesis and left–right patterning in vertebrate embryos. Nature 435, 215–220 (2005). https://doi.org/10.1038/nature03488

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