THE ANALYSIS OF PATHOGENESIS OF AMYOTROPHIC LATERAL SCLEROSIS BASED ON THE ESTABLISHMENT OF IN VITRO MOTOR NEURONAL CELL LINES

基于体外运动神经细胞系建立的肌萎缩侧索硬化症发病机制分析

基本信息

批准号：
11670156
负责人：
TANABE Yasuto
金额：
$ 2.43万
依托单位：
Osaka Bioscience Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670156/
关键词：
MOTOR NEURON AMYOTOROPHICLATERAL SCLEROSIS TRANSCRIPTION FACTORS INDUCTION P19 CELLS SPINALOORD

项目摘要

Previous works concerning the issues of neuronal diversification were able to show that the specification of neuronal identity within the CNS is controlled by the localized action of several environmental signals. These signaling molecules specify the identity of neighboring cells by inducing the expression of cell intrinsic signaling molecules, many of which are transcription factors. And these transcription factors, in turn, regulate expression of the downstream genes for the acquisition of the individual neuronal identities.Sonic hedgehog (Shh) is known to be a signaling molecule that trigger the differentiation of motor neurons, but the intervening steps between the actions of Shh and the specification of motor neuron identity were poorly understood. I have employed a differential screen of a cDNA library derived from a single early-specified motor neuron, and have identified a novel homeobox gene, MNR2, expressed by motor neuron progenitor cells and transiently by postmitotic motor neurons. The ectopic expression of MNR2 in the developing spinal cord in vivo was shown to initiate a program of motor neuron differentiation. characterized by the expression of motor neuron transcription factors, by neurotransmitter phenotype, and by axonal trajectory. These results indicate that the Shh-mediated induction of a single transcription factor, MNR2, is sufficient to direct the motor neuron differentiation.

关于神经元多样化问题的先前著作能够表明，中枢神经系统内神经元身份的规范受几种环境信号的局部作用控制。这些信号分子通过诱导细胞固有信号分子的表达来指定相邻细胞的身份，其中许多是转录因子。这些转录因子反过来又调节下游基因的表达以获取单个神经元同一性。Sonic刺猬（SHH）是一种信号分子，是一个触发运动神经元的分化的信号分子，但是SHH的动作与运动神经元同名的规范之间的间隔步骤是贫穷的。我采用了源自单个早期指定运动神经元的cDNA库的差分屏幕，并确定了由运动神经元祖细胞表达的新型同源基因MNR2，并通过蒙脱病后运动神经元瞬时。显示体内发育中的脊髓中MNR2的异位表达可引发运动神经元分化程序。以运动神经元转录因子的表达，神经递质表型和轴突轨迹为特征。这些结果表明，单个转录因子MNR2的SHH介导的诱导足以指导运动神经元分化。