Dorsally derived netrin 1 provides an inhibitory cue and elaborates the 'waiting period' for primary sensory axons in the developing spinal cord
Dorsally derived netrin 1 provides an inhibitory cue and elaborates the 'waiting period' for primary sensory axons in the developing spinal cord
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DOI：
10.1242/dev.02312
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发表时间：
2006-04-01
期刊：
影响因子：
4.6
通讯作者：
Ono, K
中科院分区：
文献类型：
--
作者：
Watanabe, K;Tamamaki, N;Ono, K
背根神经节（DRG）神经元将轴突延伸到脊髓灰质中的特定目标。在发育过程中，DRG轴突生长到脊髓背外侧边缘，并在几天的“等待期”后向背地幔层投射。Netrin 1是一种远程扩散因子，表达于发育中的神经管腹中线，对生长中的轴突具有化学吸引和化学排斥作用。Netrin 1也在脊髓背侧表达。然而，背源网络蛋白1的作用仍然是完全未知的。在这里，我们发现背网络1控制着初级感觉轴突的正确引导。在等待期，netrin 1在脊髓背侧短暂表达或上调，netrin 1的缺失导致感觉轴突（包括皮肤和本体感觉传入神经）异常投射到背地幔层。来源于脊髓背侧而非底板的Netrin 1参与了DRG轴突的正确投射。此外，netrin 1在体外抑制DRG的轴突生长。在netrin 1突变体中，Unc5c（rcm）突变体显示DRG轴突的异常侵袭。这些结果是第一个直接证据，证明脊髓背侧的网状蛋白1作为主要感觉轴突的抑制性线索，是形成感觉传入神经网络的关键信号。
Dorsal root ganglion (DRG) neurons extend axons to specific targets in the gray matter of the spinal cord. During development, DRG axons grow into the dorsolateral margin of the spinal cord and projection into the dorsal mantle layer occurs after a 'waiting period' of a few days. Netrin 1 is a long-range diffusible factor expressed in the ventral midline of the developing neural tube, and has chemoattractive and chemorepulsive effects on growing axons. Netrin 1 is also expressed in the dorsal spinal cord. However, the roles of dorsally derived netrin 1 remain totally unknown. Here, we show that dorsal netrin 1 controls the correct guidance of primary sensory axons. During the waiting period, netrin 1 is transiently expressed or upregulated in the dorsal spinal cord, and the absence of netrin 1 results in the aberrant projection of sensory axons, including both cutaneous and proprioceptive afferents, into the dorsal mantle layer. Netrin 1 derived from the dorsal spinal cord, but not the floor plate, is involved in the correct projection of DRG axons. Furthermore, netrin 1 suppresses axon outgrowth from DRG in vitro. Unc5c(rcm) mutant shows abnormal invasion of DRG axons as observed in netrin 1 mutants. These results are the first direct evidence that netrin 1 in the dorsal spinal cord acts as an inhibitory cue for primary sensory axons and is a crucial signal for the formation of sensory afferent neural networks.