联合诺奖得主 中国科学家完成蛋白功能研究

　　

生物通报道：来自上海交大的消息，上海交大生物医学研究院，系统生物学重点实验室，美国犹他大学，霍德华休斯医学院的研究人员发现一个原钙粘蛋白基因在大脑皮层发育过程中的中间神经元切线状和放射状迁移中起到重要作用。这一研究成果公布在国际著名期刊《Molecular and Cellular Biology》（《分子细胞生物学》）在最近一期（2009，29: 3045-3061）上。

文章通讯作者是犹他大学，以及上海交大的吴强博士，这项研究工作得到了美国全美癌症协会、出生缺陷基金会和中国科技部的资助。论文中小鼠构建工作是与诺贝尔奖获得者马里奥·卡佩基实验室合作完成的。 吴强实验室原钙粘蛋白功能研究取得新进展

我们的大脑包含超过一千亿个神经元细胞，这些细胞形成约一百五十万亿个特异性的突触连接。阐明人类脑神经复杂连接的发育机理和大脑学习记忆的认知功能是生命科学的巨大挑战。原钙粘蛋白家族是大脑神经元细胞膜上具有细胞特异性表达模式的细胞粘连分子。原钙粘蛋白有非常复杂的分子多样性，可能在脑发育和脑功能方面起到重要作用。

在这篇文章中，研究人员通过对基因打靶小鼠的表型分析，利用绿色荧光蛋白作为报告基因敲入原钙粘蛋白位点，发现一个原钙粘蛋白基因在大脑皮层发育过程中的中间神经元切线状和放射状迁移中起到重要作用。

原文摘要：

The Protocadherin Gene Celsr3 Is Required for Interneuron Migration in the Mouse Forebrain

Interneurons are extremely diverse in the mammalian brain and provide an essential balance for functional neural circuitry. The vast majority of murine cortical interneurons are generated in the subpallium and migrate tangentially over a long distance to acquire their final positions. By using a mouse line with a deletion of the Celsr3 (Flamingo, or Fmi1) gene and a knock-in of the green fluorescent protein reporter, we find that Celsr3, a member of the nonclustered protocadherin (Pcdh) family, is predominantly expressed in the cortical interneurons in adults and in the interneuron germinal zones in embryos. We show that Celsr3 is crucial for interneuron migration in the developing mouse forebrain. Specifically, in Celsr3 knockout mice, calretinin-positive interneurons are reduced in the developing neocortex, accumulated in the corticostriatal boundary, and increased in the striatum. Moreover, the laminar distribution of cortical calbindin-positive cells is altered. Finally, we found that expression patterns of NRG1 (neuregulin-1) and its receptor ErbB4, which are essential for interneuron migration, are changed in Celsr3 mutants. These results demonstrate that the protocadherin Celsr3 gene is essential for both tangential and radial interneuron migrations in a class-specific manner.