Mutant mice with scrambled brains: understanding the signaling pathways that control cell positioning in the CNS.
Mutant mice with scrambled brains: understanding the signaling pathways that control cell positioning in the CNS.
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DOI：
10.1101/gad.13.21.2758
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发表时间：
1999-11
影响因子：
10.5
通讯作者：
D. Rice;T. Curran
中科院分区：
文献类型：
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作者：
D. Rice;T. Curran
小鼠神经系统突变体的特征已被证明是一个非常有价值的方法来分析中枢神经系统的发展（CNS）。特别是，在过去的四年中，在鉴定和表征小鼠和人类发育中的大脑中正确细胞定位所需的基因方面取得了显著进展（D 'Arcangelo and Curran 1998;沃尔什1999）。这项工作提供了一个令人印象深刻的基因集合（表1），这些基因在神经元的径向和切向迁移中起关键作用（Pearlman et al. 1998;哈滕1999）。经典的共济失调突变小鼠reeler多年来一直作为研究影响神经元迁移和CNS组织的神经学突变的原型。这种突变的标志是大脑皮层、小脑和海马中神经元细胞结构的破坏（Caviness 1977; Rakic and Caviness 1995）。通过偶然将fos转基因插入到reeler基因座中，揭示了reeler表型的分子基础，这直接导致了reelin（Reln）基因的鉴定（D 'Arcangelo等，1995）。在短时间内，残疾人-1（Dab 1）基因被发现是负责一个卷轴样表型在人造和自然发生的小鼠突变体（豪厄尔等人，1997年b;谢尔顿等人，1997年; Ware等人，1997年），在细胞周期蛋白依赖性激酶5（Cdk 5）基因或其神经元特异性激活因子p35缺陷的小鼠中观察到相关的神经元迁移障碍（Ohshima等1996; Chae等1997）。这个佐贺最近继续报道，缺乏极低密度脂蛋白受体（VLDLR）和载脂蛋白E受体2（ApoER 2）的小鼠表现出卷轴脑的解剖学特征，Reln直接结合这些受体，激活激酶信号级联，导致Dab 1的酪氨酸磷酸化（D 'Arcangelo等，1999; Hiesberger等，1999; Trommsdorff等，1999）。这些新的发现，以及对这些基因编码的蛋白质性质的研究，正在阐述一种指导细胞在发育中的CNS中定位的分子途径。神经系统变异的老鼠
The characterization of mouse neurological mutants has proven to be an extremely valuable approach to the analysis of central nervous system development (CNS). In particular, over the past four years, remarkable progress has been made toward the identification and characterization of genes that are required for correct cell positioning in the developing brains of mice and humans (D’Arcangelo and Curran 1998; Walsh 1999). This work has provided an impressive collection of genes (Table 1) that play key roles in both the radial and tangential migration of neurons (Pearlman et al. 1998; Hatten 1999). The classical ataxic mutant mouse reeler has served for many years as a prototype for the investigation of neurological mutations affecting neuronal migration and the organization of the CNS. The hallmark of this mutant is the disruption of neuronal cytoarchitecture in the cerebral cortex, cerebellum, and hippocampus (Caviness 1977; Rakic and Caviness 1995). The molecular basis of the reeler phenotype was uncovered by the fortuitous insertion of a fos transgene into the reeler locus, which led directly to the identification of the reelin (Reln) gene (D’Arcangelo et al. 1995). In short succession, the disabled-1 (Dab1) gene was found to be responsible for a reeler-like phenotype in both man-made and naturally occurring mouse mutants (Howell et al. 1997b; Sheldon et al. 1997; Ware et al. 1997), and related neuronal migration disorders were observed in mice deficient in either the cyclin dependent kinase 5 (Cdk5) gene or its neuronal specific activator p35 (Ohshima et al. 1996; Chae et al. 1997). The saga continued recently with reports that mice lacking both the very low density lipoprotein receptor (VLDLR) and the apolipoprotein E receptor 2 (ApoER2) exhibit anatomical trademarks of the reeler brain and that Reln binds directly to these receptors, activating a kinase signaling cascade that leads to tyrosine phosphorylation of Dab1 (D’Arcangelo et al. 1999; Hiesberger et al. 1999; Trommsdorff et al. 1999). These new findings, together with studies on the properties of the proteins encoded by these genes, are elaborating a molecular pathway that directs cell positioning in the developing CNS. The neurological mutant mouse reeler