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Developmental regulation of motor neurons: Growth cone guidance, axonal branching, and synapse formation

运动神经元的发育调节：生长锥引导、轴突分支和突触形成

基本信息

批准号：
17500198
负责人：
SHOJI Wataru
金额：
$ 2.24万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500198/
关键词：
semaphorin motor neuron axon guidance zebrafish 成長円錐

项目摘要

In this grant period, we investigated roles of Sema3A in zebrafish spinal motor neurons. In zebrafish, there are two copies of sema3A genes, sema3al and sema3a2. We found these two genes functions in different steps of spinal motor neuron development. Zebrafish spinal motor neurons develop in iterative pattern that correspond to neighboring segmented somites. In each segment, caudal primary (CaP) motor neuron pioneers to exit the spinal cord just beneath its cell body, then determines the common exit points for all following motor axons. Upon the development of CaP, Sema3a2 regulates the position of its cell body and the common exit point by expressing at posterior half of newly segmented somite. Indeed, Sema3a2 knockdown embryos exhibits irregular position of CaP cell bodies and exit points that do not match with corresponding somites. Subsequently, Sema3al regulates axon guidance and branching by expressing at dorsal and ventral portion of the somite but not in between. In contrast to Sema3a2, Sema3al knockdown does not affect the position of cell body, but induce misrouting and abnormal branches on the CaP axon. These results indicate two copies of zebrafish sema3A genes subfunctions their roles during CaP development, one for the cell body positioning, and the other for the axon guidance.

在本研究期间，我们研究了Sema3A在斑马鱼脊髓运动神经元中的作用。在斑马鱼中，sema3A基因有两个拷贝，分别是sema3al和sema3a2。我们发现这两个基因在脊髓运动神经元发育的不同阶段起作用。斑马鱼的脊髓运动神经元以迭代模式发育，与相邻的节段体相对应。在每个节段中，尾侧初级（CaP）运动神经元首先离开其细胞体下方的脊髓，然后确定所有后续运动轴突的共同退出点。在CaP发育后，Sema3a2通过在新分节体后半部表达，调控其细胞体的位置和共同出口点。事实上，Sema3a2敲低的胚胎表现出CaP细胞体的不规则位置和与相应体不匹配的出口点。随后，Sema3al通过在体体的背侧和腹侧表达而不是在中间表达来调节轴突的引导和分支。与Sema3a2相反，Sema3al敲低不影响细胞体的位置，但会导致CaP轴突上的错误路线和异常分支。这些结果表明，斑马鱼sema3A基因的两个拷贝在CaP发育过程中起着亚功能，一个用于细胞体定位，另一个用于轴突引导。