The intrinsic program for migration in the developing neurons

发育中神经元迁移的内在程序

• 批准号: 16500193
• 负责人: HAYASHI Kensuke
• 金额: $ 2.3万
• 依托单位: Sophia University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500193/
• 关键词: neural development; axon elongation; cell migration; microtubules; centrosome; neuronal differentiation; 中心体; 神経細胞; 突起伸展; 形態形成; 細胞極性; 軸索伸長; カタニン

The inhibitory neurons in the mammalian cerebral cortex are born in the basal ganglia in the fetal period. We previously found that the inhibitory neurons in naonatal rat cerebral cortex have higher migratory activity when compared with excitatory neurons. In this research, we investigated when and how these neurons acquire the migratory nature.(1)During the development of brain, neurons at the basal ganglia possessed high migratory activity at embryonic 15 day. We found some cells dividing during the observation and these cells are highly migrative even before the final division, indicating that cells in the basal ganglia are migrative before neuronal differentiation.(2)As microtubules are responsible for the pulling force of cell nucleus during cell migration, we investigated the role of katanin, microtubule severing protein, in the neuronal development. When we introduced siRNA for katanin into cerebral cortical neurons to inhibit katanin expression, axon elongation but not dendrite elongation was impared. This indicate that fragmented microtubules produced by katanin is important for migration of growth cones.(3)Next we investigated the role of ninein, which is a microtubule-minus end binding protein. In the radial cells at the ventricular zone of cerebral cortex, ninein is localized at the centrosome. In differentiated neuron at the cortical plate layer, however, ninein was not localized at the centrosome and was diffusely detected in cytoplasm. This suggest that microtubules are released from centrosome after differentiation of neurons and that the released microtubules are important for the migration and axon elongation of neurons.

哺乳动物大脑皮层中的抑制性神经元在胎儿期就在基底神经节中产生。我们以前发现，与兴奋性神经元相比，新生大鼠大脑皮层中的抑制性神经元具有更高的迁移活动。在这项研究中，我们研究了这些神经元何时以及如何获得迁移性质。（1）在脑发育过程中，基底节神经元在胚胎15天具有高度的迁移活动。我们发现一些细胞分裂过程中，这些细胞是高度迁移，甚至在最后的分裂，表明在基底节细胞迁移神经元分化之前。(2)As微管在细胞迁移过程中对细胞核起牵引作用，我们研究了微管切断蛋白katanin在神经元发育中的作用。当我们将katanin的siRNA导入大脑皮层神经元以抑制katanin的表达时，轴突延长而不是树突延长是不受影响的。这表明由katanin产生的碎片化微管对于生长锥的迁移是重要的。（3）接下来，我们研究了微管负末端结合蛋白ninein的作用。在大脑皮质室区的放射状细胞中，ninein定位于中心体。而在皮层板层的分化神经元中，ninein不定位于中心体，而是弥漫性地分布于细胞质中。这表明神经元分化后中心体释放出微管，微管的释放对神经元的迁移和轴突的伸长有重要作用。

项目成果

Activation of N-methyl-D-aspartate receptor induces a shift of drebrin distribution:: Disappearance from dendritic spines and appearance in dendritic shafts

• DOI: 10.1016/j.mcn.2005.11.003
• 发表时间: 2006-03-01
• 期刊: MOLECULAR AND CELLULAR NEUROSCIENCE
• 影响因子: 3.5
• 作者: Sekino, Y;Tanaka, S;Shirao, T
• 通讯作者: Shirao, T

Identification of autotaxin as a neurite retraction-inducing factor of PC12 cells in cerebrospinal fluid and its possible sources

• DOI: 10.1111/j.1471-4159.2004.02933.x
• 发表时间: 2005-02-01
• 期刊: JOURNAL OF NEUROCHEMISTRY
• 影响因子: 4.7
• 作者: Sato, K;Malchinkhuu, E;Okajima, F
• 通讯作者: Okajima, F

培養ニューロンの軸索形成に関する研究

培养神经元轴突形成的研究

• 发表时间: 2005
• 期刊: Sophia Life Science Bulletin 23
• 作者: Furukubo-Tokunaga;K. (分担);Sekino Y et al.;Sato K.et al.;林 謙介
• 通讯作者: 林 謙介

Identification of autotaxin as a neurite retraction-inducing factor of PC12 cells in cerebrospinal fluid and its possible souces.

脑脊液中PC12细胞轴突回缩诱导因子自分泌运动因子的鉴定及其可能来源

• 发表时间: 2005
• 期刊: Journal of Neurochemistry 92
• 作者: Sato;K. et al.
• 通讯作者: K. et al.

Studies on the axon formation in mammalian neurons in culture

培养哺乳动物神经元轴突形成的研究

• 发表时间: 2005
• 期刊: Sophia Life Science Bulletin 22(in press)
• 作者: Hayashi;K.
• 通讯作者: K.