Division of Newborn Medicine, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
J Comp Neurol. 2012 Sep 1;520(13):2930-40. doi: 10.1002/cne.23076.
GPR56, one of the adhesion G-protein-coupled receptors (GPCRs), plays an important role in the development of the cerebral cortex. Mutations in GPR56 cause a severe human cortical malformation called bilateral frontoparietal polymicrogyria (BFPP), characterized by a global malformation of the cerebral cortex that most severely affects the frontal and parietal regions. To characterize the expression pattern of GPR56 in the developing cerebral cortex, we developed a mouse monoclonal antibody against mouse GPR56. We revealed that GPR56 is expressed in multiple cell types in the preplate, marginal zone, subventricular zone (SVZ), and ventricular zone (VZ). Most interestingly, the expression of GPR56 in preplate neurons showed an anterior-to-posterior gradient at embryonic day (E) 10.5-11.5. In contrast, the expression pattern of the GPR56 ligand, collagen III, revealed no visible gradient pattern. With the widespread expression of GPR56 in the developing cortex, it is difficult to draw a specific conclusion as to which of the GPR56-expressing cells are critical for human brain development. However, the correlation between GPR56 expression in neurons at E10.5-E11.5 and the anatomic distribution of the cortical malformation in both humans and mice suggests that its function in preplate neurons is indispensible.
GPR56 是黏附 G 蛋白偶联受体 (GPCR) 家族的一员，在大脑皮层发育过程中发挥着重要作用。GPR56 基因突变会导致一种严重的人类皮质畸形，称为双侧额顶多小脑回畸形 (BFPP)，其特征是大脑皮质的全面畸形，最严重的影响是额叶和顶叶区域。为了研究 GPR56 在发育中的大脑皮层中的表达模式，我们开发了一种针对小鼠 GPR56 的单克隆抗体。结果表明，GPR56 在基板、边缘区、室下区 (SVZ) 和脑室区 (VZ) 的多种细胞类型中表达。最有趣的是，E10.5-11.5 时基板神经元中的 GPR56 表达呈从前向后的梯度分布。相比之下，GPR56 配体胶原 III 的表达模式没有明显的梯度。由于 GPR56 在发育中的皮层中有广泛的表达，因此很难得出关于哪些表达 GPR56 的细胞对人类大脑发育至关重要的具体结论。然而，E10.5-E11.5 时神经元中 GPR56 的表达与人类和小鼠大脑皮质畸形的解剖分布之间的相关性表明，其在基板神经元中的功能是不可或缺的。
