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Reelin 缺乏对小鼠新皮层、海马体和杏仁核的细胞类型特异性影响。

Cell-type-specific consequences of Reelin deficiency in the mouse neocortex, hippocampus, and amygdala.

机构信息

Allen Institute for Brain Science, Seattle, Washington 98103, USA.

出版信息

J Comp Neurol. 2011 Aug 1;519(11):2061-89. doi: 10.1002/cne.22655.

Abstract

The disrupted cortical lamination phenotype in reeler mice and subsequent identification of the Reelin signaling pathway have strongly informed models of cortical development. We describe here a marker-based phenotyping approach to reexamine the cytoarchitectural consequences of Reelin deficiency, using high-throughput histology and newly identified panels of highly specific molecular markers. The resulting cell-type-level cytoarchitectural analysis revealed novel features of abnormal patterning in the male reeler mouse not obvious with less specific markers or histology. The reeler cortex has been described as a rough laminar inversion, but the data presented here are not compatible with this model. The reeler cortex is disrupted in a more complex fashion, with some regions showing a mirror-image laminar phenotype. Major rostrocaudal and cell-type-specific differences in the laminar phenotype between cortical areas are detailed. These and similar findings in hippocampus and amygdala have implications for mechanisms of normal brain development and abnormalities in neurodevelopmental disorders.

摘要

在 reeler 小鼠中,皮质层结构紊乱的表型以及随后确定的 Reelin 信号通路强烈地为皮质发育模型提供了信息。我们在这里描述了一种基于标记的表型分析方法,使用高通量组织学和新鉴定的高度特异性分子标记物重新研究 Reelin 缺乏的细胞结构后果。由此产生的细胞类型水平的细胞结构分析揭示了雄性 reeler 小鼠中异常模式的新特征,这些特征在使用不太特异的标记物或组织学检查时并不明显。reeler 皮质已被描述为粗糙的层状反转,但这里呈现的数据与该模型不兼容。reeler 皮质的破坏方式更为复杂,一些区域表现出镜像层状表型。皮质区域之间在层状表型上存在明显的前后轴和细胞类型特异性差异。这些以及在海马体和杏仁核中的类似发现,对正常大脑发育和神经发育障碍中的异常机制具有重要意义。

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