PUBLICATION

The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA

Authors
Ackerman, S.D., Garcia, C., Piao, X., Gutmann, D.H., Monk, K.R.
ID
ZDB-PUB-150122-4
Date
2015
Source
Nature communications   6: 6122 (Journal)
Registered Authors
Monk, Kelly
Keywords
Biological sciences, Neuroscience, Developmental biology
MeSH Terms
  • Microscopy, Electron, Transmission
  • Animals
  • GTP-Binding Protein alpha Subunits, G12-G13/metabolism*
  • Receptors, G-Protein-Coupled/metabolism
  • Receptors, G-Protein-Coupled/physiology*
  • Amino Acid Sequence
  • Monomeric GTP-Binding Proteins/metabolism*
  • Cell Adhesion
  • Mice, Inbred C57BL
  • Neurons/metabolism
  • Cell Proliferation
  • Male
  • Mutation
  • Oligodendroglia/metabolism*
  • Cell Differentiation
  • Female
  • Axons/metabolism
  • Myelin Sheath/metabolism
  • rho GTP-Binding Proteins/metabolism*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
  • Mice, Knockout
  • Mice
  • Molecular Sequence Data
  • Gene Expression Regulation, Developmental*
  • Sequence Homology, Amino Acid
(all 26)
PubMed
25607772 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
No images available
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
AB + MO1-gna12a + MO1-gna13a + MO1-gna13bstandard conditionsPec-fin
adgrg1stl13/+ (AB)controlPec-fin
adgrg1stl13/+ (AB)standard conditionsPec-fin
adgrg1stl13/+ (AB)standard conditionsDay 4
adgrg1stl13/+ + MO1-gna12a + MO1-gna13a + MO1-gna13b (AB)standard conditionsPec-fin
adgrg1stl13/stl13 (AB)controlPec-fin
adgrg1stl13/stl13 (AB)standard conditionsPec-fin
adgrg1stl13/stl13 (AB)standard conditionsPec-fin
adgrg1stl13/stl13 (AB)standard conditionsPec-fin
adgrg1stl13/stl13 (AB)standard conditionsProtruding-mouth
1 - 10 of 31
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mi2001TgTransgenic Insertion
    rw0130aTgTransgenic Insertion
      sl3TgTransgenic Insertion
        stl13
          		Small Deletion
          stl14
            		Small Deletion
            vu19TgTransgenic Insertion
              vu234TgTransgenic Insertion
                1 - 7 of 7
                Show
                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Target Reagent Reagent Type
                adgrg1TALEN1-adgrg1TALEN
                gna12aMO1-gna12aMRPHLNO
                gna13aMO1-gna13aMRPHLNO
                gna13bMO1-gna13bMRPHLNO
                1 - 4 of 4
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                Fish
                Antibodies
                Orthology
                Engineered Foreign Genes
                Marker Marker Type Name
                DsRed2EFGDsRed2
                EGFPEFGEGFP
                GFPEFGGFP
                KaedeEFGKaede
                mRFPEFGmRFP
                1 - 5 of 5
                Show
                Mapping
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                Citation
                Ackerman, S.D., Garcia, C., Piao, X., Gutmann, D.H., Monk, K.R. (2015) The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA. Nature communications. 6:6122.