Tremblay Marie-Eve, Riad Mustapha, Chierzi Sabrina, Murai Keith K, Pasquale Elena B, Doucet Guy
Département de Pathologie et Biologie Cellulaire, Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, Montréal, Québec, Canada.
J Comp Neurol. 2009 Feb 20;512(6):798-813. doi: 10.1002/cne.21922.
From embryonic development to adulthood, the EphA4 receptor and several of its ephrin-A or -B ligands are expressed in the hippocampus, where they presumably play distinct roles at different developmental stages. To help clarify these diverse roles in the assembly and function of the hippocampus, we examined the cellular and subcellular localization of EphA4 in postnatal rat hippocampus by light and electron microscopic immunocytochemistry. On postnatal day (P) 1, the EphA4 immunostaining was robust in most layers of CA1, CA3, and dentate gyrus and then decreased gradually, until P21, especially in the cell body layers. At the ultrastructural level, focal spots of EphA4 immunoreactivity were detected all over the plasma membrane of pyramidal and granule cells, between P1 and P14, from the perikarya to the dendritic and axonal extremities, including growth cones and filopodia. This cell surface immunoreactivity then became restricted to the synapse-associated dendritic spines and axon terminals by P21. In astrocytes, the EphA4 immunolabeling showed a similar cell surface redistribution, from the perikarya and large processes at P1-P7, to small perisynaptic processes at P14-P21. In both cell types, spots of EphA4 immunoreactivity were also detected, with an incidence decreasing with maturation, on the endoplasmic reticulum, Golgi apparatus, and vesicles, organelles involved in protein synthesis, posttranslational modifications, and transport. The cell surface evolution of EphA4 localization in neuronal and glial cells is consistent with successive involvements in the developmental movements of cell bodies first, followed by process outgrowth and guidance, synaptogenesis, and finally synaptic maintenance and plasticity.
从胚胎发育到成年期，EphA4受体及其几种ephrin - A或 - B配体在海马体中表达，它们可能在不同发育阶段发挥不同作用。为了阐明这些在海马体组装和功能中的多样作用，我们通过光镜和电镜免疫细胞化学方法研究了出生后大鼠海马体中EphA4的细胞和亚细胞定位。出生后第1天（P1），EphA4免疫染色在CA1、CA3和齿状回的大多数层中都很强，然后逐渐下降，直到P21，尤其是在细胞体层。在超微结构水平上，在P1到P14期间，从锥体细胞和颗粒细胞的胞体到树突和轴突末端，包括生长锥和丝状伪足，在整个质膜上都检测到了EphA4免疫反应性的焦点。到P21时，这种细胞表面免疫反应性仅限于与突触相关的树突棘和轴突终末。在星形胶质细胞中，EphA4免疫标记也显示出类似的细胞表面重新分布，从P1 - P7时的胞体和大的突起，到P14 - P21时的小的突触周围突起。在这两种细胞类型中，在内质网、高尔基体和囊泡（参与蛋白质合成、翻译后修饰和运输的细胞器）上也检测到了EphA4免疫反应性斑点，其发生率随着成熟而降低。EphA4在神经元和神经胶质细胞中的细胞表面定位演变与首先连续参与细胞体的发育运动、随后是突起生长和导向、突触形成，最后是突触维持和可塑性一致。
