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Reeler 突变体小鼠新皮层中不存在层特异性钙黏蛋白表达谱。

Absence of layer-specific cadherin expression profiles in the neocortex of the reeler mutant mouse.

机构信息

Institute of Anatomy I, University of Jena School of Medicine, Jena University Hospital, D-07743 Jena, Germany.

出版信息

Cereb Cortex. 2011 May;21(5):1105-17. doi: 10.1093/cercor/bhq183. Epub 2010 Sep 16.

DOI:10.1093/cercor/bhq183
PMID:20847152
Abstract

Cadherins are a superfamily of Ca(2+)-dependent cell surface glycoproteins that play a morphogenetic role in a wide variety of developmental processes. They provide a code of potentially adhesive cues for layer formation in mammalian cerebral cortex. One of the animal models used for studying corticogenesis is the reeler mouse. Previous investigations showed that radial neuronal migration is impaired in this mutant, possibly resulting in an inversion of cortical layers. However, the extent of this "outside-in" cortical layering remains unclear. In the present study, we investigated the mRNA expression of cadherins (Cdh4, Cdh6, Cdh7, Cdh8, Pcdh8, Pcdh9, Pcdh11, Pcdh17, and Pcdh19) in the cerebral cortex of wild-type (wt) mice and reeler mutants. All cadherins show a layer-specific expression profile in wt mice, but, in reeler cortex, cadherin-expressing cells are distributed widely across the radial dimension. The altered layering in reeler mutants completely disrupts the radial expression of cadherins, which is more patchy, rather than laminar. Regionalized gradient-like expression of cadherins is preserved. Our findings are compatible with a model, in which the ubiquitous dispersion of cadherin-expressing cells results from a dysgenesis of radial glial cells and a misrouting of migrating neuroblasts.

摘要

钙黏蛋白是一个依赖 Ca(2+)的细胞表面糖蛋白超家族,在广泛的发育过程中发挥形态发生作用。它们为哺乳动物大脑皮层的层形成提供了潜在的粘附线索代码。用于研究皮质发生的动物模型之一是 reeler 小鼠。先前的研究表明,这种突变体中的放射状神经元迁移受损,可能导致皮质层反转。然而,这种“从外向内”的皮质分层程度尚不清楚。在本研究中,我们研究了野生型(wt)小鼠和 reeler 突变体大脑皮层中钙黏蛋白(Cdh4、Cdh6、Cdh7、Cdh8、Pcdh8、Pcdh9、Pcdh11、Pcdh17 和 Pcdh19)的 mRNA 表达。所有钙黏蛋白在 wt 小鼠中均表现出特定于层的表达模式,但在 reeler 皮层中,表达钙黏蛋白的细胞广泛分布在放射状维度上。reeler 突变体中改变的分层完全破坏了钙黏蛋白的放射状表达,这种表达更具斑片状,而不是层状。钙黏蛋白的区域梯度样表达得以保留。我们的发现与一个模型一致,即表达钙黏蛋白的细胞的普遍分散是由于放射状神经胶质细胞的发育不良和迁移神经母细胞的错误引导所致。

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