Cyclin-dependent kinase 5 is required for normal cerebellar development.
Cyclin-dependent kinase 5 is required for normal cerebellar development.
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DOI：
10.1016/j.mcn.2012.10.007
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Ohshima T
中科院分区：
文献类型：
--
作者：
Kumazawa A;Mita N;Hirasawa M;Adachi T;Suzuki H;Shafeghat N;Kulkarni AB;Mikoshiba K;Inoue T;Ohshima T
细胞周期蛋白依赖性激酶5 （Cdk5）是一种丝氨酸/苏氨酸激酶，其激酶活性取决于其与激活亚基p35或p39的关联，p35或p39主要在神经元中表达。我们之前报道过Cdk5敲除（KO）小鼠表现出围产期死亡、神经元迁移缺陷、后脑面部运动核和下橄榄以及小脑浦肯野细胞（PCs）神经元定位异常。在这项研究中，我们重点分析了Cdk5在小脑发育中的作用。为此，我们产生了中脑-后脑特异性Cdk5条件敲除（MHB-Cdk5 KO）小鼠，因为小脑在出生后发育，而Cdk5 KO小鼠在围产期死亡。MHB-Cdk5 KO小鼠的组织学分析显示小脑明显缩小。此外，在发育中的小脑中观察到颗粒细胞（GC）向内迁移的严重紊乱。在MHB-Cdk5 KO小鼠中，浦肯野细胞（PCs）的正常树突发育受到干扰。培养的cdk5缺失的pc显示类似的树突异常。这些结果表明，Cdk5/p35在小脑发育过程中，在PCs和GCs的神经元迁移和PCs树突形成中起重要作用。
Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase, and its kinase activity is dependent upon its association with either of the activating subunits p35 or p39, which are mainly expressed in neurons. We previously reported that Cdk5 knockout (KO) mice exhibit perinatal lethality, defective neuronal migration, and abnormal positioning of neurons in the facial motor nucleus and inferior olive in the hindbrain and Purkinje cells (PCs) in the cerebellum.. In this study, we focused on the analysis of the role of Cdk5 in cerebellar development. For this purpose we generated midbrain-hindbrain-specific Cdk5 conditional knockout (MHB-Cdk5 KO) mice because the cerebellum develops postnatally, whereas Cdk5 KO mice die perinatally. Histological analysis of the MHB-Cdk5 KO mice revealed a significant size reduction of the cerebellum. In addition, profound disturbance of inward migration of granule cells (GC) was observed in the developing cerebellum. A normal dendritic development of the Purkinje cells (PCs) was disturbed in MHB-Cdk5 KO mice. Cultured Cdk5-null PCs showed similar dendritic abnormalities. These results indicate that Cdk5/p35 plays an important role in neuronal migration of PCs and GCs and dendrite formation of PCs in cerebellar development.
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DOI：
10.1073/pnas.051628498
发表时间：
2001-02-27
影响因子：
11.1
作者：
Ohshima, T;Ogawa, M;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
11.4
作者：
MAEDA, N;NIINOBE, M;MIKOSHIBA, K
通讯作者：
MIKOSHIBA, K
影响因子：
5.3
作者：
Ohshima, T;Gilmore, EC;Kulkarni, AB
通讯作者：
Kulkarni, AB
影响因子：
5.3
作者：
Ohshima, T;Ogawa, M;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
10.5
作者：
Nikolic, M;Dudek, H;Tsai, LH
通讯作者：
Tsai, LH