The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development.
The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development.
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DOI：
10.1038/ncomms7121
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发表时间：
2015-01-21
影响因子：
16.6
通讯作者：
Piao X
中科院分区：
文献类型：
--
作者：
Giera S;Deng Y;Luo R;Ackerman SD;Mogha A;Monk KR;Ying Y;Jeong SJ;Makinodan M;Bialas AR;Chang BS;Stevens B;Corfas G;Piao X
GPR56是粘附G蛋白偶联受体家族的一员，它的突变会导致一种称为双侧额顶叶多小回症（BFPP）的人脑畸形。脑磁共振成像（MRI）显示BFPP脑髓鞘缺损除了脑畸形。然而，GPR56在少突胶质细胞发育中的细胞作用尚不清楚。在这里，我们证明Gpr56的缺失导致小鼠中枢神经系统的髓鞘化降低。GPR56水平在少突胶质细胞发育的早期阶段丰富，但在髓鞘少突胶质细胞中下调。gpr56敲除小鼠表现为少突胶质前体细胞（OPC）增殖减少和RhoA活性水平降低，导致胼胝体和视神经中成熟少突胶质细胞减少和有髓鞘轴突数量减少。条件消融OPCs中的Gpr56导致成熟少突胶质细胞数量减少，这在Gpr56的组成性敲除中可见。总之，我们的数据将GPR56定义为少突胶质细胞发育的细胞自主调节因子。GPR56是粘附G蛋白偶联受体家族的一员，其突变可导致特定的人类大脑畸形和髓鞘形成缺陷，但其细胞原因尚不清楚。作者表明，小鼠Gpr56的缺失导致少突胶质前体细胞增殖减少和活性RhoA水平降低。
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. Mutations in GPR56, a member of the adhesion G protein-coupled receptor family, cause a specific human brain malformation and myelination defects but the cellular causes remain unclear. Here the authors show that loss of Gpr56 in mice leads to decreased oligodendrocyte precursor cell proliferation and diminished levels of active RhoA.
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影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
GPR56的进化动态替代剪接调节区域脑皮质模式。
DOI：
10.1126/science.1244392
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bae BI;Tietjen I;Atabay KD;Evrony GD;Johnson MB;Asare E;Wang PP;Murayama AY;Im K;Lisgo SN;Overman L;Šestan N;Chang BS;Barkovich AJ;Grant PE;Topçu M;Politsky J;Okano H;Piao X;Walsh CA
通讯作者：
Walsh CA
影响因子：
3
作者：
Colognato H;Tzvetanova ID
通讯作者：
Tzvetanova ID
DOI：
10.1242/dev.098418
发表时间：
2014-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Hoffmann SA;Hos D;Küspert M;Lang RA;Lovell-Badge R;Wegner M;Reiprich S
通讯作者：
Reiprich S
影响因子：
3.5
作者：
Jin, Zhaohui;Tietjen, Ian;Piao, Xianhua
通讯作者：
Piao, Xianhua