Netrin1 establishes multiple boundaries for axon growth in the developing spinal cord.
Netrin1 establishes multiple boundaries for axon growth in the developing spinal cord.
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Netrin1在发育中的脊髓中建立了轴突生长的多个边界。
DOI：
10.1016/j.ydbio.2017.08.001
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发表时间：
2017-10-01
影响因子：
2.7
通讯作者：
Butler SJ
中科院分区：
文献类型：
--
作者：
Varadarajan SG;Butler SJ
netrin1功能的规范模型提出，它作为一个长距离的趋化性轴突导向线索。在发育中的脊髓中，底板（FP）衍生的netrin 1被认为是一种可扩散的吸引剂，将连合轴突吸引到腹侧中线。然而，我们最近的研究表明，netrin1在FP中被定位用于轴突引导。我们已经发现netrin1在局部起作用：netrin1由心室区（VZ）的神经祖细胞（NPC）产生，并沉积在软膜表面作为引导Dcc+轴突生长的粘附基质。在这里，我们进一步证明，这netrin 1软膜基板有一个早期的作用，定向开拓脊髓轴突，指导他们向腹侧延伸。然而，随着发育的进行，连合轴突选择在VZ中netrin 1表达细胞的边界周围生长，而不是继续沿着腹侧脊髓中的netrin 1软膜基质延伸。这一观察结果表明netrin1可能提供比纯粘附更复杂的活性，netrin1表达细胞也为轴突提供生长边界。支持这种可能性，我们已经观察到，额外的netrin1表达域出现在E12.5小鼠的背根进入区（DREZ）附近，也需要塑造轴突生长。总之，我们的研究表明，netrin1提供了“常春藤”的边界：一个局部生长基质，促进轴突的延伸，同时也防止局部神经支配netrin1表达域。
The canonical model for netrin1 function proposed that it acted as a long-range chemotropic axon guidance cue. In the developing spinal cord, floor-plate (FP)-derived netrin1 was thought to act as a diffusible attractant to draw commissural axons to the ventral midline. However, our recent studies have shown that netrin1 is dispensable in the FP for axon guidance. We have rather found that netrin1 acts locally: netrin1 is produced by neural progenitor cells (NPCs) in the ventricular zone (VZ), and deposited on the pial surface as a haptotactic adhesive substrate that guides Dcc+ axon growth. Here, we further demonstrate that this netrin1 pial-substrate has an early role orienting pioneering spinal axons, directing them to extend ventrally. However, as development proceeds, commissural axons choose to grow around a boundary of netrin1 expressing cells in VZ, instead of continuing to extend alongside the netrin1 pial-substrate in the ventral spinal cord. This observation suggests netrin1 may supply a more complex activity than pure adhesion, with netrin1-expressing cells also supplying a growth boundary for axons. Supporting this possibility, we have observed that additional domains of netrin1 expression arise adjacent to the dorsal root entry zone (DREZ) in E12.5 mice that are also required to sculpt axonal growth. Together, our studies suggest that netrin1 provides “hederal” boundaries: a local growth substrate that promotes axon extension, while also preventing local innervation of netrin1-expressing domains.
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影响因子：
64.5
作者：
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