Cyclin-dependent kinase 5/p35 contributes synergistically with reelin/Dab1 to the positioning of facial branchiomotor and inferior olive neurons in the developing mouse hindbrain
Cyclin-dependent kinase 5/p35 contributes synergistically with reelin/Dab1 to the positioning of facial branchiomotor and inferior olive neurons in the developing mouse hindbrain
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DOI：
10.1523/jneurosci.22-10-04036.2002
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发表时间：
2002-05-15
影响因子：
5.3
通讯作者：
Mikoshiba, K
中科院分区：
文献类型：
--
作者：
Ohshima, T;Ogawa, M;Mikoshiba, K
细胞周期蛋白依赖性激酶 5 (Cdk5)/p35 是一种丝氨酸/苏氨酸激酶，其活性主要在有丝分裂后神经元中检测到。缺乏 Cdk5/p35 的小鼠表现出大脑和小脑皮质神经元的迁移缺陷。在这项研究中，我们证明，虽然大多数脑干核处于正确的位置，但面神经的运动核位于异位，下橄榄神经元无法正确定位，导致 Cdk5-/- 小鼠后脑缺乏其特征结构。尽管这些神经元的迁移有缺陷，但在 Cdk5-/- 小鼠中，面神经从脑干的轴突出口和下小脑轴突的投射似乎没有变化。 Cdk5-/- 后脑中的缺陷神经元迁移通过 Cdk5 转基因的神经元特异性表达得到挽救。由于在 reeler 和 Dab1 突变小鼠中已报道了这些结构的发育缺陷，因此我们分析了 p35 和 Dab1 的双无效突变体，并在这些小鼠中发现了更广泛的 VII 运动核异位。这些结果表明，Cdk5/p35 和 Reelin 信号传导调节发育中的小鼠后脑中神经元迁移的选择性模式。
Cyclin-dependent kinase 5 (Cdk5)/p35 is a serine/threonine kinase, and its activity is detected primarily in postmitotic neurons. Mice lacking Cdk5/p35 display migration defects of the cortical neurons in the cerebrum and cerebellum. In this study, we demonstrate that although most brainstem nuclei are found in their proper positions, the motor nucleus of the facial nerve is ectopically located and neurons of the inferior olive fail to position correctly, resulting in the lack of their characteristic structures in the hindbrain of Cdk5-/- mice. Despite the defective migration of these neurons, axonal exits of the facial nerve from brainstem and projections of the inferior cerebellar axons appear unchanged in Cdk5-/- mice. Defective neuronal migration in Cdk5-/- hindbrain was rescued by the neuron-specific expression of Cdk5 transgene. Because developmental defects of these structures have been reported in reeler and Dab1 mutant mice, we analyzed the double-null mutants of p35 and Dab1 and found more extensive ectopia of VII motor nuclei in these mice. These results indicate that Cdk5/p35 and Reelin signaling regulates the selective mode of neuronal migration in the developing mouse hindbrain.