@article{4de02e3c412944aca1da8c424c351abf,
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.",
author = "Stefanie Giera and Yiyu Deng and Rong Luo and Ackerman, {Sarah D.} and Amit Mogha and Monk, {Kelly R.} and Yanqin Ying and Jeong, {Sung Jin} and Manabu Makinodan and Bialas, {Allison R.} and Chang, {Bernard S.} and Beth Stevens and Gabriel Corfas and Xianhua Piao",
note = "Funding Information: We thank Drs Christopher A. Walsh and Jacques Michaud for providing the brain MRI images of a reported BFPP patient; Dr Charles Stiles for anti-Olig2 antibody and the Pdgfra plasmid for in situ hybridization; Dr J. Bradley Zuchero for consultation on immunopanning of OPCs; Mouse Gene Manipulation Core at Boston Children{\textquoteright}s Hospital (NIHP30-HD 18655) for their assistance in generating floxed Gpr56 mice. This research was supported in part by NINDS grant R01 NS057536 (X.P.); William Randolph Hearst Fund Award (S.G., R.L., & S.-J.J.); Leonard and Isabelle Goldenson Research Fellowship (R.L.); NINDS grant F31 NS087801; NINDS grant R01 NS079445 (K.R.M.); and Cerebral Palsy International Research Foundation Award (X.P.). Funding Information: We thank Drs Christopher A. Walsh and Jacques Michaud for providing the brain MRI images of a reported BFPP patient; Dr Charles Stiles for anti-Olig2 antibody and the Pdgfra plasmid for in situ hybridization; Dr J. Bradley Zuchero for consultation on immunopanning of OPCs; Mouse Gene Manipulation Core at Boston Children''s Hospital (NIHP30-HD 18655) for their assistance in generating floxed Gpr56 mice. This research was supported in part by NINDS grant R01 NS057536 (X.P.); William Randolph Hearst Fund Award (S.G., R.L., & S.-J.J.); Leonard and Isabelle Goldenson Research Fellowship (R.L.); NINDS grant F31 NS087801; NINDS grant R01 NS079445 (K.R.M.); and Cerebral Palsy International Research Foundation Award (X.P.).",
year = "2015",
month = jan,
day = "21",
doi = "10.1038/ncomms7121",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}