Synaptic-like Vesicles Facilitate Pioneer Axon Invasion
Synaptic-like Vesicles Facilitate Pioneer Axon Invasion
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DOI：
10.1016/j.cub.2019.06.078
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发表时间：
2019-08
期刊：
影响因子：
9.2
通讯作者：
Evan L. Nichols;Cody J. Smith
中科院分区：
文献类型：
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作者：
Evan L. Nichols;Cody J. Smith
在成熟的神经回路中，突触囊泡对神经元的通讯是不可或缺的。突触囊泡生物发生必须与轴突导航同时发生，但突触囊泡是否在突触发生前的电路形成中起功能作用尚不清楚。在这里，我们使用延时成像和斑马鱼的转基因来可视化突触样囊泡在背根神经节先锋轴突导航中的作用。我们发现，当先锋轴突在背根进入区突破脊髓边界时，突触样囊泡在中央生长锥中积累。细胞特异性破伤风毒素表达抑制囊泡释放导致先锋轴突寻径缺陷和脊髓入口改变。我们进一步表明，基质金属蛋白酶（MMP）mmp14是先锋轴突穿越脊髓边界所必需的，并且通过超分辨率显微镜，与突触囊泡一起定位在边界上。同时操纵肌动蛋白重组表明肌动蛋白重塑驱动囊泡释放和随后的MMP活性。总之，这些数据表明，在轴突导航的特定点上，突触样囊泡作为生长锥微环境的调节剂发挥着不可或缺的作用。
Synaptic vesicles are indispensable for neuronal communication in mature circuits. Synaptic vesicle biogenesis must be concurrent with axon navigation for synaptogenesis, but whether synaptic vesicles are functionally employed in circuit formation before synaptogenesis is poorly understood. Here, we use time-lapse imaging and transgenesis in zebrafish to visualize the role of synaptic-like vesicles in navigation of dorsal root ganglia pioneer axons. We identify that synaptic-like vesicles accumulate in the central growth cone as the pioneer axon breaches the spinal boundary at the dorsal root entry zone. Inhibition of vesicle release with cell-specific tetanus toxin expression results in pioneer axon pathfinding defects and altered spinal entry. We further show that the matrix metalloproteinase (MMP)mmp14ais required in pioneer axons to navigate across the boundary of the spinal cord and, with super-resolution microscopy, is positioned with synaptic vesicles at the boundary. Manipulations of concurrent actin reorganization reveal that actin remodeling drives vesicle release and subsequent MMP activity. Together, these data point to an indispensable role for synaptic-like vesicles at specific points in axon navigation as regulators of growth cone microenvironment.