Molecular analysis of axon repulsion by the notochord
Molecular analysis of axon repulsion by the notochord
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DOI：
10.1242/dev.00327
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发表时间：
2003-03-01
期刊：
影响因子：
4.6
通讯作者：
Tannahill, D
中科院分区：
文献类型：
--
作者：
Anderson, CNG;Ohta, K;Tannahill, D
在脊髓周围神经系统的发育过程中，初级感觉轴突的初始轨迹在很大程度上取决于轴突排斥剂的作用。我们以前已经表明，背根神经节两侧的组织，脊索躺在内侧和dermamyotomes躺在侧面，是分泌的分子，防止轴突进入不适当的领土的来源。尽管有证据表明SEMA 3A有助于皮肌刀的驱避活性，但脊索分泌的活性的性质仍未确定。我们采用表达克隆策略来寻找脊索分泌的轴突排斥剂，并确定SEMA 3A作为候选排斥剂。此外，使用不同的轴突群体的光谱，以测定脊索的活动，连同神经纤毛蛋白/Fc受体试剂，以阻止脑信号蛋白的活性在胶原蛋白凝胶测定，我们表明，SEMA 3A可能有助于脊索介导的排斥。交感神经轴突，通常避免中线在体内也排斥，在一定程度上，由一个基于脑信号蛋白的脊索活动。虽然我们的研究结果牵连semaphorin信号介导的排斥脊索，排斥早期背根神经节轴突时，使用neuropilin/Fc试剂仅部分阻断。此外，对SEMA 3A不敏感的视网膜轴突也被脊索排斥。我们的结论是，多个因素共同作用，以指导轴突在这个系统中，和进一步的脊索驱避剂仍有待确定。
During development of the amniote peripheral nervous system, the initial trajectory of primary sensory axons is determined largely by the action of axon repellents. We have shown previously that tissues flanking dorsal root ganglia, the notochord lying medially and the dermamyotomes lying laterally, are sources of secreted molecules that prevent axons from entering inappropriate territories. Although there is evidence suggesting that SEMA3A contributes to the repellent activity of the dermamyotome, the nature of the activity secreted by the notochord remains undetermined. We have employed an expression cloning strategy to search for axon repellents secreted by the notochord, and have identified SEMA3A as a candidate repellent. Moreover, using a spectrum of different axon populations to assay the notochord activity, together with neuropilin/Fc receptor reagents to block semaphorin activity in collagen gel assays, we show that SEMA3A probably contributes to notochord-mediated repulsion. Sympathetic axons that normally avoid the midline in vivo are also repelled, in part, by a semaphorin-based notochord activity. Although our results implicate semaphorin signalling in mediating repulsion by the notochord, repulsion of early dorsal root ganglion axons is only partially blocked when using neuropilin/Fc reagents. Moreover, retinal axons, which are insensitive to SEMA3A, are also repelled by the notochord. We conclude that multiple factors act in concert to guide axons in this system, and that further notochord repellents remain to be identified.