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

Stefanie Giera, Yiyu Deng, Rong Luo, Sarah D. Ackerman, Amit Mogha, Kelly Monk, Yanqin Ying, Sung Jin Jeong, Manabu Makinodan, Allison R. Bialas, Bernard S. Chang, Beth Stevens, Gabriel Corfas, Xianhua Piao

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish (US)
Article number7121
JournalNature Communications
Volume6
DOIs
StatePublished - Jan 21 2015
Externally publishedYes

Fingerprint

regulators
Oligodendroglia
G-Protein-Coupled Receptors
brain
Brain
adhesion
Adhesion
proteins
knockout mice
cells
axons
central nervous system
Cell proliferation
nerves
Neurology
mutations
Ablation
Magnetic resonance imaging
ablation
mice

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development. / Giera, Stefanie; Deng, Yiyu; Luo, Rong; Ackerman, Sarah D.; Mogha, Amit; Monk, Kelly; Ying, Yanqin; Jeong, Sung Jin; Makinodan, Manabu; Bialas, Allison R.; Chang, Bernard S.; Stevens, Beth; Corfas, Gabriel; Piao, Xianhua.

In: Nature Communications, Vol. 6, 7121, 21.01.2015.

Research output: Contribution to journalArticle

Giera, S, Deng, Y, Luo, R, Ackerman, SD, Mogha, A, Monk, K, Ying, Y, Jeong, SJ, Makinodan, M, Bialas, AR, Chang, BS, Stevens, B, Corfas, G & Piao, X 2015, 'The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development', Nature Communications, vol. 6, 7121. https://doi.org/10.1038/ncomms7121
Giera, Stefanie ; Deng, Yiyu ; Luo, Rong ; Ackerman, Sarah D. ; Mogha, Amit ; Monk, Kelly ; Ying, Yanqin ; Jeong, Sung Jin ; Makinodan, Manabu ; Bialas, Allison R. ; Chang, Bernard S. ; Stevens, Beth ; Corfas, Gabriel ; Piao, Xianhua. / The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development. In: Nature Communications. 2015 ; Vol. 6.
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