GPR56 regulates pial basement membrane integrity and cortical lamination
GPR56 regulates pial basement membrane integrity and cortical lamination
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DOI：
10.1523/jneurosci.0853-08.2008
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发表时间：
2008-05-28
影响因子：
5.3
通讯作者：
Piao, Xianhua
中科院分区：
文献类型：
--
作者：
Li, Shihong;Jin, Zhaohui;Piao, Xianhua
GPR56是黏附性G蛋白偶联受体家族的成员，其具有一个包含GPS（G蛋白水解位点）结构域的大的细胞外区域。GPR56基因的功能缺失突变会导致一种特定的人类脑部畸形，称为双侧额顶叶多小脑回畸形（BFPP）。BFPP是一种放射学诊断，其组织病理学仍不清楚。这项研究表明，小鼠Gpr56基因的缺失会导致大脑皮质中的神经元异位，一种鹅卵石样皮质畸形。鹅卵石样皮质的发育有四个关键事件，即软脑膜基底膜（BM）缺陷、放射状胶质细胞终足异常附着、卡哈尔 - 雷济厄斯细胞定位错误以及神经元过度迁移。通过详细的时间进程分析，我们揭示主要的致病事件可能是软脑膜基底膜的破损。我们进一步表明，GPR56大量存在于放射状胶质细胞终足中。此外，一种假定的GPR56配体定位在边缘区或上方的细胞外基质中。这些观察结果提供了令人信服的证据，表明GPR56在皮质发育过程中对调节软脑膜基底膜的完整性起作用。
GPR56 is a member of the family of adhesion G-protein-coupled receptors that have a large extracellular region containing a GPS (G-protein proteolytic site) domain. Loss-of-function mutations in the GPR56 gene cause a specific human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). BFPP is a radiological diagnosis and its histopathology remains unclear. This study demonstrates that loss of the mouse Gpr56 gene leads to neuronal ectopia in the cerebral cortex, a cobblestone-like cortical malformation. There are four crucial events in the development of cobblestone cortex, namely defective pial basement membrane (BM), abnormal anchorage of radial glial endfeet, mislocalized Cajal -Retzius cells, and neuronal overmigration. By detailed time course analysis, we reveal that the leading causal events are likely the breaches in the pial BM. We show further that GPR56 is present in abundance in radial glial endfeet. Furthermore, a putative ligand of GPR56 is localized in the marginal zone or overlying extracellular matrix. These observations provide compelling evidence that GPR56 functions in regulating pial BM integrity during cortical development.