Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers
Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers
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DOI：
10.1016/j.neuron.2007.01.028
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发表时间：
2007-02-15
期刊：
影响因子：
16.2
通讯作者：
Fujisawa, Hajime
中科院分区：
文献类型：
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作者：
Suto, Fumikazu;Tsuboi, Miu;Fujisawa, Hajime
海马苔藓纤维优先投射到透明层，透明层是CA3椎体上区域最近端的板层。支配这种椎板限制投射的分子机制仍不清楚。我们研究了信号素受体Plexin-A2和Plexin-A4及其配体跨膜信号素Sema6A的突变小鼠苔藓纤维的投射模式。我们发现，Plexin-A2缺乏导致苔藓纤维从锥体上区向锥体下区和锥体内区移动，而Plexin-A4缺乏导致苔藓纤维在CA3内不适当地扩散。我们还报道，丛状蛋白-A2功能丧失表型在基因上被Sema-6A功能丧失抑制。基于这些结果，我们提出了苔藓纤维的片层受限投射模型：苔藓纤维上丛状蛋白A4的表达阻止了它们进入表达Sema6A的CA3的半月板上区域，并将它们限制在最近端，在那里Sema6A的排斥活动被丛状蛋白-A2减弱。
Hippocampal mossy fibers project preferentially to the stratum lucidum, the proximal-most lamina of the suprapyramidal region of CA3. The molecular mechanisms that govern this lamina-restricted projection are still unknown. We examined the projection pattern of mossy fibers in mutant mice for semaphorin receptors plexin-A2 and plexin-A4, and their ligand, the transmembrane semaphorin Sema6A. We found that plexin-A2 deficiency causes a shift of mossy fibers from the suprapyramidal region to the infra- and intrapyramidal regions, while plexin-A4 deficiency induces inappropriate spreading of mossy fibers within CA3. We also report that the plexin-A2 loss-of-function phenotype is genetically suppressed by Sema-6A loss of function. Based on these results, we propose a model for the lamina-restricted projection of mossy fibers: the expression of plexinA4 on mossy fibers prevents them from entering the Sema6A-expressing suprapyramidal region of CA3 and restricts them to the proximal-most part, where Sema6A repulsive activity is attenuated by plexin-A2.