Otal R, Burgaya F, Frisén J, Soriano E, Martínez A
Department of Cell Biology, University of Barcelona and Institut de Recerca Biomèdica, Parc Científic de Barcelona, E-08028 Barcelona, Spain.
Neuroscience. 2006 Aug 11;141(1):109-21. doi: 10.1016/j.neuroscience.2006.03.052. Epub 2006 May 11.
Entorhinal and commissural/associational projections show a non-overlapping distribution in the hippocampus proper and the dentate gyrus. The expression of Ephrins and their Eph receptors in the developing hippocampus indicates that this family of axonal guidance molecules may modulate the formation of these connections. Here we focused on the role of the ephrin-A5 ligand in the development of the main hippocampal afferents. In situ hybridization showed that ephrin-A5 mRNA was detected mainly in the principal cells of the hippocampus proper and in the dentate gyrus throughout postnatal development. Immunocytochemical analyses revealed prominent expression of the EphA3 receptor, a putative receptor for ephrin-A5, in the main cells and the neuropil of the developing hippocampus. Tracing experiments in ephrin-A5(-/-) mice showed that commissural projections were transiently altered in the hippocampus proper at P5, but they were mistargeted throughout the postnatal development in the dentate gyrus. Immunocytochemistry with anti-calbindin antibodies revealed that the dentate mossy fiber projection was not altered in ephrin-A5(-/-) mice. Electron microscopy studies showed alterations in the density of synapses and spines in commissural/associational layers, but not in entorhinal layers, and in the mossy fibers in these animals. Taken together, these findings indicate that ephrin-A5 signaling is involved in the formation and maturation of synapses in the hippocampus.
内嗅皮层和连合/联合投射在海马本部和齿状回中显示出不重叠的分布。Ephrins及其Eph受体在发育中的海马中的表达表明，这个轴突导向分子家族可能调节这些连接的形成。在这里，我们重点研究了ephrin-A5配体在主要海马传入纤维发育中的作用。原位杂交显示，在整个出生后发育过程中，ephrin-A5 mRNA主要在海马本部的主要细胞和齿状回中被检测到。免疫细胞化学分析显示，EphA3受体（一种推测的ephrin-A5受体）在发育中的海马的主要细胞和神经毡中有显著表达。对ephrin-A5基因敲除小鼠的追踪实验表明，连合投射在出生后第5天在海马本部有短暂改变，但在齿状回的整个出生后发育过程中都出现了投射错误。用抗钙结合蛋白抗体进行的免疫细胞化学显示，在ephrin-A5基因敲除小鼠中齿状苔藓纤维投射没有改变。电子显微镜研究显示，在这些动物的连合/联合层而非内嗅层以及苔藓纤维中，突触和棘突的密度发生了改变。综上所述，这些发现表明ephrin-A5信号通路参与了海马中突触的形成和成熟。
