Cadherin-8 and N-cadherin differentially regulate pre- and postsynaptic development of the hippocampal mossy fiber pathway
Cadherin-8 and N-cadherin differentially regulate pre- and postsynaptic development of the hippocampal mossy fiber pathway
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DOI：
10.1002/hipo.20395
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发表时间：
2008-01-01
期刊：
影响因子：
3.5
通讯作者：
Benson, Deanna L.
中科院分区：
文献类型：
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作者：
Bekirov, Iddil H.;Nagy, Vanja;Benson, Deanna L.
细胞在发育过程中部分地通过特定经典钙粘蛋白的选择性表面表达来分类为区域和组。在神经系统中，基于钙粘蛋白的分类可以定义轴突束，将轴突和树突乔木限制在特定区域或层，并且可以编码突触特异性的某些方面。基本模型是传入神经及其靶标共同表达特定的钙粘蛋白，从而提供同源钙粘蛋白结合的识别码。然而，大多数神经元表达多种钙粘蛋白，并且尚不清楚多种钙粘蛋白在塑造神经回路方面是否都具有相似的作用。在这里，我们询问两种这样的钙粘蛋白，钙粘蛋白-8和N-钙粘蛋白，如何影响海马苔藓纤维的引导和分化。使用器官型海马培养物，我们发现 cadherin-8 调节苔藓纤维束状和靶向，但对 CA3 树突影响不大。相比之下，N-钙粘蛋白调节苔藓纤维束，但对轴突生长和靶向影响很小。然而，N-钙粘蛋白对于 CA3 树突树枝化至关重要。两种钙粘蛋白都是形成适当数量的突触前末梢所必需的。从机制上讲，这两种钙粘蛋白的这种差异作用理论上可以反映与不同的细胞内结合伙伴的偶联。然而，我们发现两种钙粘蛋白都与齿状回 (DG) 中的 β-连环蛋白结合。这表明钙粘蛋白可能参与β-连环蛋白下游不同的细胞内信号级联，选择不同的细胞外结合配偶体，或靶向不同的亚细胞结构域。我们的研究结果共同表明，cadherin-8 和 N-cadherin 对于生成苔藓纤维通路至关重要，但它们对传入和靶标分化的贡献不同，从而在突触回路的组装中相互补充。 (C) 2007 Wiley-Liss, Inc.
Cells sort into regions and groups in part by their selective surface expression of particular classic cadherins during development. In the nervous system, cadherin-based sorting can define axon tracts, restrict axonal and dendritic arbors to particular regions or layers, and may encode certain aspects of synapse specificity. The underlying model has been that afferents and their targets hold in common the expression of a particular cadherin, thereby providing a recognition code of homophilic cadherin binding. However, most neurons express multiple cadherins, and it is not clear whether multiple cadherins all act similarly in shaping neural circuitry. Here we asked how two such cadherins, cadherin-8 and N-cadherin, influence the guidance and differentiation of hippocampal mossy fibers. Using organotypic hippocampal cultures, we find that cadherin-8 regulates mossy fiber fasciculation and targeting, but has little effect on CA3 dendrites. In contrast, N-cadherin regulates mossy fiber fasciculation, but has little impact on axonal growth and targeting. However, N-cadherin is essential for CA3 dendrite arborization. Both cadherins are required for formation of proper numbers of presynaptic terminals. Mechanistically, such differential actions of these two cadherins could, in theory, reflect coupling to distinct intracellular binding partners. However, we find that both cadherins bind beta-catenin in dentate gyrus (DG). This suggests that cadherins may engage different intracellular signaling cascades downstream of beta-catenin, coopt different extracellular binding partners, or target distinct subcellular domains. Together our findings demonstrate that cadherin-8 and N-cadherin are critical for generating the mossy fiber pathway, but that each contributes differentially to afferent and target differentiation, thereby complementing one another in the assembly of a synaptic circuit. (C) 2007 Wiley-Liss, Inc.