title: The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA.
abstract: In the vertebrate central nervous system, myelinating oligodendrocytes are postmitotic and derive from proliferative oligodendrocyte precursor cells (OPCs). The molecular mechanisms that govern oligodendrocyte development are incompletely understood, but recent studies implicate the adhesion class of G protein-coupled receptors (aGPCRs) as important regulators of myelination. Here, we use zebrafish and mouse models to dissect the function of the aGPCR Gpr56 in oligodendrocyte development. We show that gpr56 is expressed during early stages of oligodendrocyte development. In addition, we observe a significant reduction of mature oligodendrocyte number and myelinated axons in gpr56 zebrafish mutants. This reduction results from decreased OPC proliferation, rather than increased cell death or altered neural precursor differentiation potential. Finally, we show that these functions are mediated by Gα12/13 proteins and Rho activation. Together, our data establish Gpr56 as a regulator of oligodendrocyte development.
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 Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Garcia
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
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
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
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein
chemical_list: D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020559:Monomeric GTP-Binding Proteins; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C524781:Adgrg1 protein, mouse; C526380:RhoA protein, mouse; C549425:rhoab protein, zebrafish