Miyasaka Nobuhiko, Knaut Holger, Yoshihara Yoshihiro
Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Development. 2007 Jul;134(13):2459-68. doi: 10.1242/dev.001958. Epub 2007 May 30.
Positioning neurons in the right places and wiring axons to the appropriate targets are essential events for establishment of neural circuits. In the zebrafish olfactory system, precursors of olfactory sensory neurons (OSNs) assemble into a compact cluster to form the olfactory placode. Subsequently, OSNs differentiate and extend their axons to the presumptive olfactory bulb with high precision. In this study, we aim to elucidate the molecular mechanism underlying these two developmental processes. cxcr4b, encoding a chemokine receptor, is expressed in the migrating olfactory placodal precursors, and cxcl12a (SDF-1a), encoding a ligand for Cxcr4b, is expressed in the abutting anterior neural plate. The expression of cxcr4b persists in the olfactory placode at the initial phase of OSN axon pathfinding. At this time, cxcl12a is expressed along the placode-telencephalon border and at the anterior tip of the telencephalon, prefiguring the route and target of OSN axons, respectively. Interfering with Cxcl12a/Cxcr4b signaling perturbs the assembly of the olfactory placode, resulting in the appearance of ventrally displaced olfactory neurons. Moreover, OSN axons frequently fail to exit the olfactory placode and accumulate near the placode-telencephalon border in the absence of Cxcr4b-mediated signaling. These data indicate that chemokine signaling contributes to both the olfactory placode assembly and the OSN axon pathfinding in zebrafish.
将神经元定位在正确的位置并将轴突连接到合适的靶标是神经回路建立的关键事件。在斑马鱼嗅觉系统中，嗅觉感觉神经元（OSN）的前体细胞聚集形成一个紧密的簇，构成嗅觉基板。随后，OSN分化并将其轴突高精度地延伸至假定的嗅球。在本研究中，我们旨在阐明这两个发育过程背后的分子机制。编码趋化因子受体的cxcr4b在迁移中的嗅觉基板前体细胞中表达，而编码Cxcr4b配体的cxcl12a（SDF-1a）在相邻的前神经板中表达。在OSN轴突寻路的初始阶段，cxcr4b在嗅觉基板中持续表达。此时，cxcl12a沿着基板-端脑边界以及端脑的前端表达，分别预示着OSN轴突的路径和靶标。干扰Cxcl12a/Cxcr4b信号会扰乱嗅觉基板的组装，导致出现腹侧移位的嗅觉神经元。此外，在缺乏Cxcr4b介导的信号时，OSN轴突常常无法离开嗅觉基板并在基板-端脑边界附近聚集。这些数据表明趋化因子信号对斑马鱼的嗅觉基板组装和OSN轴突寻路都有作用。
