The Protocadherin Gene Celsr3 Is Required for Interneuron Migration in the Mouse Forebrain
The Protocadherin Gene Celsr3 Is Required for Interneuron Migration in the Mouse Forebrain
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DOI：
10.1128/mcb.00011-09
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发表时间：
2009-03
影响因子：
5.3
通讯作者：
G. Ying;Sen Wu;Ruiqing Hou;Wei Huang;M. Capecchi;Qiang Wu
中科院分区：
文献类型：
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作者：
G. Ying;Sen Wu;Ruiqing Hou;Wei Huang;M. Capecchi;Qiang Wu
摘要哺乳动物大脑中的中间神经元是极其多样的，为功能性神经回路提供了必要的平衡。绝大多数小鼠皮层中间神经元产生于下腭，并在长距离上切向迁移以获得它们的最终位置。通过使用一个删除的Celsr 3（火烈鸟，或Fmi 1）基因和敲入的绿色荧光蛋白报告的小鼠系，我们发现，Celsr 3，非集群原钙粘蛋白（Pcdh）家族的成员，主要是在成年人的皮层中间神经元和胚胎中的中间神经元生发区表达。我们表明，Celsr 3是至关重要的发育中的小鼠前脑的中间神经元迁移。具体而言，在Celsr 3基因敲除小鼠中，钙视黄蛋白阳性中间神经元在发育中的新皮质中减少，在皮质纹状体边界中积累，并在纹状体中增加。此外，皮层钙结合蛋白阳性细胞的层状分布被改变。最后，我们发现，NRG 1（神经调节蛋白-1）及其受体ErbB 4，这是必不可少的神经元迁移的表达模式，改变Celsr 3突变体。这些结果表明，原钙粘蛋白Celsr 3基因是必要的切向和径向interneuron迁移类特异性的方式。
ABSTRACT 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.