Characterization of G protein-coupled receptor 56 protein expression in the mouse developing neocortex.

Characterization of G protein-coupled receptor 56 protein expression in the mouse developing neocortex.
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DOI:
10.1002/cne.23076
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发表时间:
2012-09-01
影响因子:
2.5
通讯作者:
Piao, Xianhua
Piao, Xianhua
中科院分区:
医学3区
文献类型:
--
作者:
Jeong, Sung-Jin;Luo, Rong;Li, Shihong;Strokes, Natalie;Piao, Xianhua

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GPR56是黏附性G蛋白偶联受体(GPCRs)之一,在大脑皮层的发育中起重要作用。GPR56的突变会导致一种严重的人类大脑皮层畸形,称为双侧额顶叶多小脑回畸形(BFPP),其特征是大脑皮层的整体性畸形,对额叶和顶叶区域的影响最为严重。为了描述GPR56在发育中的大脑皮层的表达模式,我们研制了一种针对小鼠GPR56的小鼠单克隆抗体。我们发现GPR56在大脑皮层前板、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,在胚胎期(E)10.5 - 11.5天,前板神经元中的表达呈现从前到后的梯度。相比之下,GPR56的配体胶原蛋白III的表达模式没有明显的梯度模式。由于GPR56在发育中的皮层广泛表达,很难就哪些表达GPR56的细胞对人类大脑发育至关重要得出具体结论。然而,在E10.5 - E11.5时神经元中GPR56的表达与人类和小鼠大脑皮层畸形的解剖分布之间的相关性表明,它在前板神经元中的功能是不可或缺的。
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 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.
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