3D mapping of neuronal migration in the embryonic mouse brain with magnetic resonance microimaging.
3D mapping of neuronal migration in the embryonic mouse brain with magnetic resonance microimaging.
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DOI：
10.1016/j.neuroimage.2015.04.010
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发表时间：
2015-07-01
期刊：
影响因子：
5.7
通讯作者：
Turnbull DH
中科院分区：
文献类型：
--
作者：
Deans AE;Wadghiri YZ;Aristizábal O;Turnbull DH
哺乳动物大脑发育的一个显著特征是胚胎发生过程中神经祖细胞（NP）的广泛迁移。孕中期小鼠腹前脑中出生的NP细胞提供了一个显著的例子，这些细胞随后长途迁移到它们在皮层和嗅球中的最终位置。以前的研究使用二维组织学方法，使得难以分析三维（3D）迁移模式。与组织学不同，磁共振微成像（micro-MRI）是一种非破坏性的、定量的、固有的3D成像方法，用于分析小鼠胚胎。为了利用微mri对迁移的NP细胞进行定位，在子宫内超声引导下靶向注射微米大小的氧化铁颗粒（MPIO），在内侧（MGE）和外侧（LGE）神经节突起处原位标记细胞。注射后5-6天进行体外微mri和组织学检查，表明MPIO对迁移的NP群体进行了磁性标记，从而实现了标记细胞的3D可视化和自动分割。利用该方法分析了MGE和LGE的不同迁移模式，并构建了每个祖先区域的喙尾迁移图。此外，在Nkx2.1−/−胚胎中观察到异常的迁移表型，最明显的是来自Nkx2.1−/−LGE的皮质神经元显著增加。综上所述，这些结果表明MPIO标记和微mri为分析正常和突变小鼠胚胎脑的3D细胞迁移模式提供了一种有效而有力的方法。
A prominent feature of the developing mammalian brain is the widespread migration of neural progenitor (NP) cells during embryogenesis. A striking example is provided by NP cells born in the ventral forebrain of mid-gestation stage mice, which subsequently migrate long distances to their final positions in the cortex and olfactory bulb. Previous studies have used two-dimensional histological methods, making it difficult to analyze three-dimensional (3D) migration patterns. Unlike histology, magnetic resonance microimaging (micro-MRI) is a non-destructive, quantitative and inherently 3D imaging method for analyzing mouse embryos. To allow mapping of migrating NP cells with micro-MRI, cells were labeled in situ in the medial (MGE) and lateral (LGE) ganglionic eminences, using targeted in utero ultrasound-guided injection of micron-sized particles of iron-oxide (MPIO). Ex vivo micro-MRI and histology were then performed 5-6 days after injection, demonstrating that the MPIO had magnetically labeled the migrating NP populations, which enabled 3D visualization and automated segmentation of the labeled cells. This approach was used to analyze the distinct patterns of migration from the MGE and LGE, and to construct rostral-caudal migration maps from each progenitor region. Furthermore, abnormal migratory phenotypes were observed in Nkx2.1−/− embryos, most notably a significant increase in cortical neurons derived from the Nkx2.1−/− LGE. Taken together, these results demonstrate that MPIO labeling and micro-MRI provide an efficient and powerful approach for analyzing 3D cell migration patterns in the normal and mutant mouse embryonic brain.
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