Genetic Mosaic Dissection of Lis1 and Ndel1 in Neuronal Migration
Genetic Mosaic Dissection of Lis1 and Ndel1 in Neuronal Migration
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DOI：
10.1016/j.neuron.2010.09.027
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发表时间：
2010-11-18
期刊：
影响因子：
16.2
通讯作者：
Luo, Liqun
中科院分区：
文献类型：
--
作者：
Hippenmeyer, Simon;Youn, Yong Ha;Luo, Liqun
新生神经元协调迁移到其预期目标层是发育中大脑中神经回路组装的先决条件。进化上保守的 LIS1/NDEL1 复合物对于哺乳动物大脑皮层的神经元迁移至关重要。 LIS1 和 NDEL1 蛋白的细胞质性质表明它们自主调节神经元迁移细胞。在这里，我们将双标记嵌合分析 (MADM) 扩展到 Lis1、Ndel1 和 14-3-3 epsilon（编码 LIS1/NDEL1 信号伴侣）所在的小鼠 11 号染色体。对镶嵌动物中稀疏且独特标记的突变细胞的分析揭示了这三个基因的不同细胞自主功能。 Lis1 以剂量依赖性方式调节神经元迁移效率，而 Ndel1 对于神经元迁移的特定的、先前未表征的后期步骤：进入目标层至关重要。与之前的 Lis1 和 Ndel1 基因扰动的比较也表明这些蛋白质在调节神经元迁移方面具有令人惊讶的细胞非自主功能。
Coordinated migration of newly born neurons to their prospective target laminae is a prerequisite for neural circuit assembly in the developing brain. The evolutionarily conserved LIS1/NDEL1 complex is essential for neuronal migration in the mammalian cerebral cortex. The cytoplasmic nature of LIS1 and NDEL1 proteins suggest that they regulate neuronal migration cell autonomously. Here, we extend mosaic analysis with double markers (MADM) to mouse chromosome 11 where Lis1, Ndel1, and 14-3-3 epsilon (encoding a LIS1/NDEL1 signaling partner) are located. Analyses of sparse and uniquely labeled mutant cells in mosaic animals reveal distinct cell-autonomous functions for these three genes. Lis1 regulates neuronal migration efficiency in a dose-dependent manner, while Ndel1 is essential for a specific, previously uncharacterized, late step of neuronal migration: entry into the target lamina. Comparisons with previous genetic perturbations of Lis1 and Ndel1 also suggest a surprising degree of cell-nonautonomous function for these proteins in regulating neuronal migration.