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

Handle URI:
http://hdl.handle.net/10754/627206
Title:
The ancestral retinoic acid receptor was a low-affinity sensor triggering neuronal differentiation
Authors:
Handberg-Thorsager, Mette ( 0000-0002-3908-7233 ) ; Gutierrez-Mazariegos, Juliana; Arold, Stefan T. ( 0000-0001-5278-0668 ) ; Kumar Nadendla, Eswar; Bertucci, Paola Y. ( 0000-0002-4116-7689 ) ; Germain, Pierre; Tomançak, Pavel; Pierzchalski, Keely ( 0000-0002-2456-0382 ) ; Jones, Jace W. ( 0000-0003-0460-0380 ) ; Albalat, Ricard ( 0000-0003-0282-9595 ) ; Kane, Maureen A. ( 0000-0002-5525-9170 ) ; Bourguet, William; Laudet, Vincent ( 0000-0003-4022-4175 ) ; Arendt, Detlev ( 0000-0001-7833-050X ) ; Schubert, Michael ( 0000-0002-2341-712X )
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Handberg-Thorsager M, Gutierrez-Mazariegos J, Arold ST, Kumar Nadendla E, Bertucci PY, et al. (2018) The ancestral retinoic acid receptor was a low-affinity sensor triggering neuronal differentiation. Science Advances 4: eaao1261. Available: http://dx.doi.org/10.1126/sciadv.aao1261.
Publisher:
American Association for the Advancement of Science (AAAS)
Journal:
Science Advances
Issue Date:
22-Feb-2018
DOI:
10.1126/sciadv.aao1261
PubMed ID:
29492455
Type:
Article
ISSN:
2375-2548
Sponsors:
We are indebted to N. Robert, M. Sémon, O. Simakov, and T. Larsson for help with bioinformatic analyses. K. Achim, P. Mejstrik, and G. Holzer supported pharmacological treatments, whole-mount in situ hybridization experiments, and transactivation assays, respectively. We also thank S. P. Singh for providing plasmids and K. Skouloudaki for discussions. This work was financed by the European Molecular Biology Laboratory (to M.H.-T., P.Y.B., and D.A.), the Ministerio de Ciencia e Innovación (ES-2008-236 to M.H.-T. and BFU2010-14875 to R.A.), the European Research Council (HOURGLASS no. 260746 to M.H.-T. and P.T. and BrainEvoDevo no. 294810 to P.Y.B. and D.A.), the King Abdullah University of Science and Technology (to S.T.A.), the Ministerio de Economía y Competitividad (BIO2015-67358-C2-1-P to R.A.), the French Infrastructure for Integrated Structural Biology program (ANR-10-INBS-05 to W.B.), and the Agence Nationale de la Recherche (ANR-11-JSV2-002-01 to M.S.).
Additional Links:
http://advances.sciencemag.org/content/4/2/eaao1261.full
Appears in Collections:
Articles; Bioscience Program; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorHandberg-Thorsager, Metteen
dc.contributor.authorGutierrez-Mazariegos, Julianaen
dc.contributor.authorArold, Stefan T.en
dc.contributor.authorKumar Nadendla, Eswaren
dc.contributor.authorBertucci, Paola Y.en
dc.contributor.authorGermain, Pierreen
dc.contributor.authorTomançak, Pavelen
dc.contributor.authorPierzchalski, Keelyen
dc.contributor.authorJones, Jace W.en
dc.contributor.authorAlbalat, Ricarden
dc.contributor.authorKane, Maureen A.en
dc.contributor.authorBourguet, Williamen
dc.contributor.authorLaudet, Vincenten
dc.contributor.authorArendt, Detleven
dc.contributor.authorSchubert, Michaelen
dc.date.accessioned2018-02-27T09:00:13Z-
dc.date.available2018-02-27T09:00:13Z-
dc.date.issued2018-02-22en
dc.identifier.citationHandberg-Thorsager M, Gutierrez-Mazariegos J, Arold ST, Kumar Nadendla E, Bertucci PY, et al. (2018) The ancestral retinoic acid receptor was a low-affinity sensor triggering neuronal differentiation. Science Advances 4: eaao1261. Available: http://dx.doi.org/10.1126/sciadv.aao1261.en
dc.identifier.issn2375-2548en
dc.identifier.pmid29492455-
dc.identifier.doi10.1126/sciadv.aao1261en
dc.identifier.urihttp://hdl.handle.net/10754/627206-
dc.description.abstractRetinoic 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.en
dc.description.sponsorshipWe are indebted to N. Robert, M. Sémon, O. Simakov, and T. Larsson for help with bioinformatic analyses. K. Achim, P. Mejstrik, and G. Holzer supported pharmacological treatments, whole-mount in situ hybridization experiments, and transactivation assays, respectively. We also thank S. P. Singh for providing plasmids and K. Skouloudaki for discussions. This work was financed by the European Molecular Biology Laboratory (to M.H.-T., P.Y.B., and D.A.), the Ministerio de Ciencia e Innovación (ES-2008-236 to M.H.-T. and BFU2010-14875 to R.A.), the European Research Council (HOURGLASS no. 260746 to M.H.-T. and P.T. and BrainEvoDevo no. 294810 to P.Y.B. and D.A.), the King Abdullah University of Science and Technology (to S.T.A.), the Ministerio de Economía y Competitividad (BIO2015-67358-C2-1-P to R.A.), the French Infrastructure for Integrated Structural Biology program (ANR-10-INBS-05 to W.B.), and the Agence Nationale de la Recherche (ANR-11-JSV2-002-01 to M.S.).en
dc.publisherAmerican Association for the Advancement of Science (AAAS)en
dc.relation.urlhttp://advances.sciencemag.org/content/4/2/eaao1261.fullen
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.titleThe ancestral retinoic acid receptor was a low-affinity sensor triggering neuronal differentiationen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentBioscience Programen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalScience Advancesen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDevelopmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69012 Heidelberg, Germany.en
dc.contributor.institutionMolecular 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.en
dc.contributor.institutionCentre de Biochimie Structurale, Inserm, CNRS, Université de Montpellier, 29 Rue de Navacelles, 34090 Montpellier, France.en
dc.contributor.institutionMax Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.en
dc.contributor.institutionDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 North Pine Street, Baltimore, MD 21201, USA.en
dc.contributor.institutionDepartament de Genètica, Microbiologia i Estadística, Institut de Recerca de la Biodiversitat (IRBio), Facultat de Biologia, Universitat de Barcelona, Avinguda Diagonal 643, 08028 Barcelona, Spain.en
dc.contributor.institutionCentre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.en
dc.contributor.institutionSorbonne 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.en
kaust.authorArold, Stefan T.en

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