Ephrin-A5 Regulates the Formation of the Ascending Midbrain Dopaminergic Pathways
Ephrin-A5 Regulates the Formation of the Ascending Midbrain Dopaminergic Pathways
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DOI：
10.1002/dneu.20685
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发表时间：
2009-01-01
影响因子：
3
通讯作者：
Zhou, Renping
中科院分区：
文献类型：
--
作者：
Cooper, Margaret A.;Kobayashi, Kazuto;Zhou, Renping
黑质和中脑腹侧被盖区的多巴胺能神经元分别投射到尾壳核和伏隔核，建立中纹状体通路和中边缘通路。然而，这些途径发展的潜在机制还没有被很好地理解。在目前的研究中，EPHA5受体及其相应的配基eaffinA5被证明调节多巴胺能轴突的生长，并影响中脑多巴胺能通路的形成。用β-半乳糖苷酶取代EPHA5胞浆结构域的突变小鼠，在中脑腹侧被盖区和黑质都检测到EPHA5蛋白的表达。在纹状体的背外侧区和腹内侧区都发现了eaffin-A5，这表明它在介导多巴胺能轴突与靶点的相互作用中发挥了作用。在体外共培养实验中，在肾上腺素-A5存在的情况下，多巴胺能神经元延长了轴突。此外，在缺乏eaffin-A5的小鼠中，逆行追踪研究显示，向纹状体发送轴突的神经元较少。这些观察表明，EPhin-A配体和EphA受体之间的相互作用促进了中脑多巴胺能轴突的生长和纹状体的靶向。(C)2008Wiley期刊公司开发神经生物学69：36-46.2009
Dopaininergic neurons from the substantia nigra and the ventral tegmental area of the midbrain project to the caudate/putamen and nucleus accumbens, respectively, establishing the mesostriatal and the mesolimbic pathways. However, the mechanisms underlying the development of these pathways are not well understood. In the current study, the EphA5 receptor and its corresponding ligand, ephrinA5, were shown to regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. Using a strain of mutant mice in which the EphA5 cytoplasmic domain was replaced with beta-galactosidase, EphA5 protein expression was detected in both the ventral tegmental area and the substantia nigra of the midbrain. Ephrin-A5 was found in both the dorsolateral and the ventromedial regions of the striatum, suggesting a role in mediating dopaminergic axon-target interactions. In the presence of ephrin-A5, dopaminergic neurons extended longer neurites in in vitro coculture assays. Furthermore, in mice lacking ephrin-A5, retrograde tracing studies revealed that fewer neurons sent axons to the striatum. These observations indicate that the interactions between ephrin-A ligands and EphA receptors promote growth and targeting of the midbrain dopaminergic axons to the striatum. (C) 2008 Wiley Periodicals, Inc. Develop Neurobiol 69:36-46.2009