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Sci Adv. 2018 Feb 21;4(2):eaao1261. doi: 10.1126/sciadv.aao1261. eCollection 2018 Feb.

The ancestral retinoic acid receptor was a low-affinity sensor triggering neuronal differentiation.

Author information

1
Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69012 Heidelberg, Germany.
2
Molecular Zoology Team, Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Institut National de la Recherche Agronomique, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
3
King Abdullah University of Science and Technology, Center for Computational Bioscience Research, Division of Biological and Environmental Sciences and Engineering, Thuwal 23955-6900, Saudi Arabia.
4
Centre de Biochimie Structurale, Inserm, CNRS, Université de Montpellier, 29 Rue de Navacelles, 34090 Montpellier, France.
5
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
6
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 North Pine Street, Baltimore, MD 21201, USA.
7
Departament de Genètica, Microbiologia i Estadística, Institut de Recerca de la Biodiversitat (IRBio), Facultat de Biologia, Universitat de Barcelona, Avinguda Diagonal 643, 08028 Barcelona, Spain.
8
Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.
9
Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, CNRS, Laboratoire de Biologie du Développement de Villefranche-sur-Mer, Observatoire Océanologique de Villefranche-sur-Mer, 181 Chemin du Lazaret, 06230 Villefranche-sur-Mer, France.

Abstract

Retinoic acid (RA) is an important intercellular signaling molecule in vertebrate development, with a well-established role in the regulation of hox genes during hindbrain patterning and in neurogenesis. However, the evolutionary origin of the RA signaling pathway remains elusive. To elucidate the evolution of the RA signaling system, we characterized RA metabolism and signaling in the marine annelid Platynereis dumerilii, a powerful model for evolution, development, and neurobiology. Binding assays and crystal structure analyses show that the annelid retinoic acid receptor (RAR) binds RA and activates transcription just as vertebrate RARs, yet with a different ligand-binding pocket and lower binding affinity, suggesting a permissive rather than instructive role of RA signaling. RAR knockdown and RA treatment of swimming annelid larvae further reveal that the RA signal is locally received in the medial neuroectoderm, where it controls neurogenesis and axon outgrowth, whereas the spatial colinear hox gene expression in the neuroectoderm remains unaffected. These findings suggest that one early role of the new RAR in bilaterian evolution was to control the spatially restricted onset of motor and interneuron differentiation in the developing ventral nerve cord and to indicate that the regulation of hox-controlled anterior-posterior patterning arose only at the base of the chordates, concomitant with a high-affinity RAR needed for the interpretation of a complex RA gradient.

PMID:
29492455
PMCID:
PMC5821490
DOI:
10.1126/sciadv.aao1261
[Indexed for MEDLINE]
Free PMC Article

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