Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, Prague, Czech Republic.
Neuroscience. 2013 Jun 14;240:39-53. doi: 10.1016/j.neuroscience.2013.02.048. Epub 2013 Mar 1.
The mouse Dach1 gene, involved in the development of the neocortex and the hippocampus, is expressed by neural stem cells (NSCs) during early neurogenesis, and its expression also continues in a subpopulation of cells in the dorsal part of the lateral ventricles (LV) of the adult mouse brain. In this study we aimed to elucidate the role of Dach1-expressing cells in adult neurogenesis/gliogenesis under physiological as well as post-ischemic conditions, employing transgenic mice in which the expression of green fluorescent protein (GFP) is controlled by the D6 promotor of the mouse Dach1 gene. A neurosphere-forming assay of GFP⁺ cells isolated from the dorsal part of the LV was carried out with subsequent differentiation in vitro. To elucidate the neurogenic/gliogenic potential of GFP⁺ cells in the dorsal part of the LV, in situ immunohistochemical/electrophysiological analyses of GFP⁺ cells in adult sham-operated brains (controls) and those after middle cerebral artery occlusion (MCAo) were performed. The GFP⁺ cells isolated from the dorsal part of the LV of controls formed neurospheres and differentiated solely into a glial phenotype, while those isolated after MCAo also gave rise to cells with the properties of neuronal precursors. In situ analyses revealed that GFP⁺ cells express the phenotype of adult NSCs or neuroblasts in controls as well as following ischemia. Following MCAo we found a significantly increased number of GFP⁺ cells expressing doublecortin as well as a number of GFP⁺ cells migrating through the rostral migratory stream into the olfactory bulb, where they probably differentiated into calretinin⁺ interneurons. Collectively, our results suggest the involvement of the mouse Dach1 gene in adult neurogenesis; cells expressing this gene exhibit the properties of adult NSCs or neuroblasts and respond to MCAo by enhanced neurogenesis.
鼠 Dach1 基因参与新皮层和海马体的发育，在早期神经发生过程中由神经干细胞（NSCs）表达，其表达也在成年小鼠大脑侧脑室（LV）背侧的一个细胞亚群中持续表达。在这项研究中，我们旨在阐明 Dach1 表达细胞在生理和缺血后条件下对成年神经发生/神经胶质发生的作用，方法是使用 GFP 表达受鼠 Dach1 基因 D6 启动子控制的转基因小鼠。对从 LV 背侧分离的 GFP⁺细胞进行神经球形成测定，并进行体外分化。为了阐明 LV 背侧 GFP⁺细胞的神经发生/神经胶质发生潜能，对成年假手术大脑（对照）和大脑中动脉闭塞（MCAo）后 GFP⁺细胞进行原位免疫组织化学/电生理分析。从对照组 LV 背侧分离的 GFP⁺细胞形成神经球，并仅分化为神经胶质表型，而从 MCAo 后分离的细胞也产生具有神经元前体特性的细胞。原位分析表明，GFP⁺细胞在对照和缺血后表达成年 NSCs 或神经母细胞的表型。MCAo 后，我们发现 GFP⁺细胞表达双皮质蛋白的数量显著增加，并且 GFP⁺细胞的数量通过前脑迁移流迁移到嗅球，在那里它们可能分化为 calretinin⁺中间神经元。总之，我们的结果表明鼠 Dach1 基因参与成年神经发生；表达该基因的细胞表现出成年 NSCs 或神经母细胞的特性，并通过增强神经发生对 MCAo 做出反应。
