title: Developmental and adult expression patterns of the G-protein-coupled receptor GPR88 in the rat: Establishment of a dual nuclear-cytoplasmic localization.
abstract: GPR88 is a neuronal cerebral orphan G-protein-coupled receptor (GPCR) that has been linked to various psychiatric disorders. However, no extensive description of its localization has been provided so far. Here, we investigate the spatiotemporal expression of the GPR88 in prenatal and postnatal rat tissues by using in situ hybridization and immunohistochemistry. GPR88 protein was initially detected at embryonic day 16 (E16) in the striatal primordium. From E16-E20 to adulthood, the highest expression levels of both protein and mRNA were observed in striatum, olfactory tubercle, nucleus accumbens, amygdala, and neocortex, whereas in spinal cord, pons, and medulla GPR88 expression remains discrete. We observed an intracellular redistribution of GPR88 during cortical lamination. In the cortical plate of the developing cortex, GPR88 presents a classical GPCR plasma membrane/cytoplasmic localization that shifts, on the day of birth, to nuclei of neurons progressively settling in layers V to II. This intranuclear localization remains throughout adulthood and was also detected in monkey and human cortex as well as in the amygdala and hypothalamus of rats. Apart from the central nervous system, GPR88 was transiently expressed at high levels in peripheral tissues, including adrenal cortex (E16-E21) and cochlear ganglia (E19-P3), and also at moderate levels in retina (E18-E19) and spleen (E21-P7). The description of the GPR88 anatomical expression pattern may provide precious functional insights into this novel receptor. Furthermore, the GRP88 nuclear localization suggests nonclassical GPCR modes of action of the protein that could be relevant for cortical development and psychiatric disorders. J. Comp. Neurol. 524:2776-2802, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: INSERM UMR894, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, 75014, Paris, France.|Neurology-Psychiatry Department, Pierre Fabre Research Institute, 81100, Castres, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Massart
authors.affiliation: INSERM UMR894, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, 75014, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Mignon
authors.affiliation: INSERM UMR894, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, 75014, Paris, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stanic
authors.affiliation: INSERM UMR894, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, 75014, Paris, France.
authors.forename: Paola
authors.initials: P
authors.lastname: Munoz-Tello
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg, CNRS, INSERM, 67400, Illkirch-Graffenstaden, France.
authors.forename: Jerôme A J
authors.initials: JA
authors.lastname: Becker
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg, CNRS, INSERM, 67400, Illkirch-Graffenstaden, France.
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
authors.affiliation: INSERM UMR894, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, 75014, Paris, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Darmon
authors.affiliation: Neurology-Psychiatry Department, Pierre Fabre Research Institute, 81100, Castres, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sokoloff
authors.affiliation: INSERM UMR894, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, 75014, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.
authors.forename: Jorge
authors.initials: J
authors.lastname: Diaz
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002467:Cell Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: C000606984:Gpr88 protein, rat; D043562:Receptors, G-Protein-Coupled
keywords: development; neocortex; nuclear GPCRs; nucleus