Contributors: European Molecular Biology Laboratory Heidelberg (EMBL); Institut de Génomique Fonctionnelle de Lyon (IGFL); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Centre National de la Recherche Scientifique (CNRS); King Abdullah University of Science and Technology Saudi Arabia (KAUST); Centre de Biochimie Structurale Montpellier (CBS); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS); Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG); Max-Planck-Gesellschaft; University of Maryland Baltimore County (UMBC); University of Maryland System; Departament de Genètica, Microbiologia i Estadística Barcelona, Spain; Universitat de Barcelona (UB)-Institut de Recerca de la Biodiversitat - Biodiversity Research Institute Barcelona, Spain (IRBio UB); Universitat de Barcelona (UB); Centre for Organismal Studies Heidelberg, Germany; Universität Heidelberg Heidelberg = Heidelberg University; Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV); Observatoire océanologique de Villefranche-sur-mer (OOVM); Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS); Sorbonne Université (SU); ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010); ANR-11-JSV2-0002,RAvolution,RAvolution : l'histoire (r)évolutionnaire d'une voie de signalisation morphogène-dépendante(2011)
نبذة مختصرة : International audience ; 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.
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