Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Neuroscience. 2010 May 5;167(2):312-22. doi: 10.1016/j.neuroscience.2010.01.035. Epub 2010 Jan 28.
Continuous proliferation occurs in the adult subventricular zone (SVZ) of the lateral ventricles throughout life. In the SVZ, progenitor cells differentiate into neuroblasts, which migrate tangentially along the rostral migratory stream (RMS) to reach their final destination in the olfactory bulb. These progenitor cells mature and integrate into the existing neural network of the olfactory bulb. Long distance migration of neuroblasts in the RMS requires a highly dynamic cytoskeleton with the ability to respond to surrounding stimuli. Radixin is a member of the ERM (Ezrin, Radixin, Moesin) family, which connect the actin cytoskeleton to the extracellular matrix through transmembrane proteins. The membrane-cytoskeleton linker proteins of the ERM family may regulate cellular events with a high demand on cytoskeleton plasticity, such as cell motility. Recently, specific expression of the ERM protein ezrin was shown in the RMS. Radixin however has not been characterized in this region. Here we used immunohistochemistry and confocal microscopy to examine the expression of radixin in the different cell types of the adult subventricular zone niche and in the RMS. Our findings indicate that radixin is strongly expressed in neuroblasts of the adult RMS and subventricular zone, and also in Olig2-positive cells. We also demonstrate the presence of radixin in the cerebral cortex, striatum, cerebellum, thalamus, hippocampus as well as the granular and periglomerular layers of the olfactory bulb. Our studies also reveal the localization of radixin in neurosphere culture studies and we reveal the specificity of our labeling using Western blotting. The expression pattern demonstrated here suggests a role for radixin in neuronal migration and differentiation in the adult RMS. Understanding how adult neuronal migration is regulated is of importance for the development of new therapeutic interventions using endogenous repair for neurodegenerative diseases.
成年侧脑室室下区(SVZ)持续增殖发生在整个生命过程中。在 SVZ 中,祖细胞分化为神经母细胞,它们沿着嗅球的前向迁移流(RMS)沿切线迁移,到达它们的最终目的地。这些祖细胞成熟并整合到嗅球的现有神经网络中。神经母细胞在 RMS 中的远距离迁移需要一个具有高度动态的细胞骨架,能够对周围刺激做出反应。根蛋白是 ERM(Ezrin、Radixin、Moesin)家族的成员,该家族通过跨膜蛋白将细胞骨架连接到细胞外基质上。ERM 家族的膜细胞骨架连接蛋白可能调节对细胞骨架可塑性要求很高的细胞事件,例如细胞迁移。最近,ERM 蛋白 ezrin 在 RMS 中特异性表达。然而,Radixin 在该区域尚未得到描述。在这里,我们使用免疫组织化学和共聚焦显微镜检查 Radixin 在成年 SVZ 龛和 RMS 中不同细胞类型中的表达。我们的研究结果表明,Radixin 在成年 RMS 和 SVZ 的神经母细胞中以及 Olig2 阳性细胞中强烈表达。我们还证明 Radixin 存在于大脑皮层、纹状体、小脑、丘脑、海马体以及嗅球的颗粒层和旁肾小球层中。我们的研究还揭示了 Radixin 在神经球培养研究中的定位,并且我们使用 Western blot 证明了我们标记的特异性。这里展示的表达模式表明 Radixin 在成年 RMS 中的神经元迁移和分化中发挥作用。了解成年神经元迁移是如何被调控的,对于利用内源性修复来治疗神经退行性疾病的新治疗干预措施的发展具有重要意义。