title: The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development.
abstract: Mutations in GPR56, a member of the adhesion G protein-coupled receptor family, cause a human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Magnetic resonance imaging (MRI) of BFPP brains reveals myelination defects in addition to brain malformation. However, the cellular role of GPR56 in oligodendrocyte development remains unknown. Here, we demonstrate that loss of Gpr56 leads to hypomyelination of the central nervous system in mice. GPR56 levels are abundant throughout early stages of oligodendrocyte development, but are downregulated in myelinating oligodendrocytes. Gpr56-knockout mice manifest with decreased oligodendrocyte precursor cell (OPC) proliferation and diminished levels of active RhoA, leading to fewer mature oligodendrocytes and a reduced number of myelinated axons in the corpus callosum and optic nerves. Conditional ablation of Gpr56 in OPCs leads to a reduced number of mature oligodendrocytes as seen in constitutive knockout of Gpr56. Together, our data define GPR56 as a cell-autonomous regulator of oligodendrocyte development.
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Giera
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Ackerman
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Mogha
authors.affiliation: 1] Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA [2] Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Monk
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Ying
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.affiliation: 1] F.M. Kirby Neurobiology Center, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Manabu
authors.initials: M
authors.lastname: Makinodan
authors.affiliation: 1] F.M. Kirby Neurobiology Center, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Bialas
authors.affiliation: Comprehensive Epilepsy Center, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Chang
authors.affiliation: 1] F.M. Kirby Neurobiology Center, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Stevens
authors.affiliation: 1] F.M. Kirby Neurobiology Center, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Corfas
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Piao
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D009900:Optic Nerve / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D013629:Tamoxifen / Q000737:chemistry; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D043562:Receptors, G-Protein-Coupled; D013629:Tamoxifen; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C524781:Adgrg1 protein, mouse; C526380:RhoA protein, mouse