Roles of semaphorin-6B and plexin-A2 in lamina-restricted projection of hippocampal mossy fibers.
Roles of semaphorin-6B and plexin-A2 in lamina-restricted projection of hippocampal mossy fibers.
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DOI：
10.1523/jneurosci.0073-10.2010
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发表时间：
2010-05-19
期刊：
影响因子：
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通讯作者：
Fujisawa H
中科院分区：
文献类型：
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作者：
Tawarayama H;Yoshida Y;Suto F;Mitchell KJ;Fujisawa H
海马苔藓纤维优先投射至CA3区锥体上区最近端、透明层和CA3c锥下区最近端。然而，控制苔藓纤维片层限制投射的分子机制还没有完全了解。我们先前研究了神经排斥蛋白Sema6A(Sema6A)及其受体Plexin-A2(PlxnA2)和Plexin-A4(PlxnA4)在苔藓纤维投射中的功能，并提出表达PlxnA4的苔藓纤维主要被阻止进入表达Sema6A的CA3锥体上和锥体下区域，但允许生长到表达Sema6A的近端区域，在那里Sema6A的排斥活性被PlxnA2竞争性地抑制。在本研究中，我们证明了另一类6类跨膜信号素Semaphorin-6B(Sema6B)在CA3中表达，并在体外以PlxnA4依赖的方式排斥苔藓纤维。在Sema6B基因缺陷小鼠中，有几条苔藓纤维异常地投射到放射层和东方层。在Sema6A和Sema6B双基因敲除小鼠中，苔藓纤维的数量增加，表明Sema6A和Sema6B在调节苔藓纤维的正确投射方面具有相加的作用。PlxnA2不抑制Sema6B反应，但本身促进苔藓纤维的生长。在这些结果的基础上，我们提出，苔藓纤维被Sema6A和Sema6B排斥与被PlxnA2和未知分子(S)吸引之间的平衡决定了苔藓纤维可以支配的区域。
Hippocampal mossy fibers project preferentially to the proximal-most lamina of the suprapyramidal region of CA3, the stratum lucidum, and proximal-most parts of the infrapyrmidal region of CA3c. Molecular mechanisms that govern the lamina-restricted projection of mossy fibers, however, have not been fullly understood. We previously studied functions of a neural repellent Semaphorin-6A (Sema6A), a class 6 transmembrane semaphorin, and its receptors, plexin-A2 (PlxnA2) and plexin-A4 (PlxnA4), in mossy fiber projection, and have proposed that PlxnA4-expressing mossy fibers are principally prevented from entering the Sema6A-expressing supra- and infrapyramidal regions of CA3, but permitted to grow into proximal parts of the regions, where repulsive activity of Sema6A is competitively suppressed by PlxnA2. In the present study we demonstrate that Semaphorin-6B (Sema6B), another class 6 transmembrane semaphorin, is expressed in CA3, and repels mossy fibers in a PlxnA4-dependent manner in vitro. In Sema6B-deficient mice several mossy fibers aberrantly project to the stratum radiatum and the stratum oriens. The number of abberant mossy fibers is increased in Sema6A;Sema6B double knockout mice, indicating that Sema6A and Sema6B function additively to regulate proper projection of mossy fibers. PlxnA2 does not suppress the Sema6B response, but itself promotes growth of mossy fibers. Based on these results, we propose that the balance between mossy fiber repulsion by Sema6A and Sema6B and attraction by PlxnA2 and unknown molecule(s) prescribes the areas permissive for mossy fibers to innervate.