Giera Stefanie, Deng Yiyu, Luo Rong, Ackerman Sarah D, Mogha Amit, Monk Kelly R, Ying Yanqin, Jeong Sung-Jin, Makinodan Manabu, Bialas Allison R, Chang Bernard S, Stevens Beth, Corfas Gabriel, Piao Xianhua
Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Nat Commun. 2015 Jan 21;6:6121. doi: 10.1038/ncomms7121.
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.
粘附G蛋白偶联受体家族成员GPR56的突变会导致一种名为双侧额顶叶多小脑回（BFPP）的人脑畸形。BFPP患者脑部的磁共振成像（MRI）显示，除了脑畸形外，还存在髓鞘形成缺陷。然而，GPR56在少突胶质细胞发育中的细胞作用仍不清楚。在此，我们证明Gpr56缺失会导致小鼠中枢神经系统髓鞘形成减少。在少突胶质细胞发育的早期阶段，GPR56水平丰富，但在正在形成髓鞘的少突胶质细胞中表达下调。Gpr56基因敲除小鼠表现为少突胶质前体细胞（OPC）增殖减少，活性RhoA水平降低，导致胼胝体和视神经中成熟少突胶质细胞数量减少，有髓轴突数量减少。在OPC中条件性敲除Gpr56会导致成熟少突胶质细胞数量减少，这与Gpr56组成型敲除的情况一致。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。
Zotero 插件
