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Nat Commun. 2015 Jan 21;6:6121. doi: 10.1038/ncomms7121.

The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development.

Author information

1
Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
2
Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
3
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.
4
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.
5
Comprehensive Epilepsy Center, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.

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.

PMID:
25607655
PMCID:
PMC4302951
DOI:
10.1038/ncomms7121
[Indexed for MEDLINE]
Free PMC Article

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