title: Developmental expression of orphan G protein-coupled receptor 50 in the mouse brain.
abstract: Mental disorders have a complex etiology resulting from interactions between multiple genetic risk factors and stressful life events. Orphan G protein-coupled receptor 50 (GPR50) has been identified as a genetic risk factor for bipolar disorder and major depression in women, and there is additional genetic and functional evidence linking GPR50 to neurite outgrowth, lipid metabolism, and adaptive thermogenesis and torpor. However, in the absence of a ligand, a specific function has not been identified. Adult GPR50 expression has previously been reported in brain regions controlling the HPA axis, but its developmental expression is unknown. In this study, we performed extensive expression analysis of GPR50 and three protein interactors using rt-PCR and immunohistochemistry in the developing and adult mouse brain. Gpr50 is expressed at embryonic day 13 (E13), peaks at E18, and is predominantly expressed by neurons. Additionally we identified novel regions of Gpr50 expression, including brain stem nuclei involved in neurotransmitter signaling: the locus coeruleus, substantia nigra, and raphe nuclei, as well as nuclei involved in metabolic homeostasis. Gpr50 colocalizes with yeast-two-hybrid interactors Nogo-A, Abca2, and Cdh8 in the hypothalamus, amygdala, cortex, and selected brain stem nuclei at E18 and in the adult. With this study, we identify a link between GPR50 and neurotransmitter signaling and strengthen a likely role in stress response and energy homeostasis.
authors.affiliation: Medical Genetics Section, University of Edinburgh, Institute of Genetics and Molecular Medicine, Molecular Medicine Centre, Crewe Road, Edinburgh EH2 4XU, United Kingdom.
authors.forename: Ellen
authors.initials: E
authors.lastname: Grünewald
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Tew
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Pippa A
authors.initials: PA
authors.lastname: Thomson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D018377:Neurotransmitter Agents / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: C509755:Gpr50 receptor, mouse; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D043562:Receptors, G-Protein-Coupled