Widespread expression of netrin-1 by neurons and oligodendrocytes in the adult mammalian spinal cord
Widespread expression of netrin-1 by neurons and oligodendrocytes in the adult mammalian spinal cord
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DOI：
10.1523/jneurosci.21-11-03911.2001
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发表时间：
2001-06-01
影响因子：
5.3
通讯作者：
Kennedy, TE
中科院分区：
文献类型：
--
作者：
Manitt, C;Colicos, MA;Kennedy, TE
Netrins是一个分泌蛋白家族，在神经发育过程中作为趋化性轴突指导信号发挥作用。在这里，我们证明了Netrin-1在成年大鼠脊髓中的表达水平与胚胎中枢神经系统中的表达水平相似。相反，Netrin-3也在胚胎脊髓中表达，但在成年鼠中没有检测到。原位杂交结果显示，成年大鼠脊髓白质和灰质细胞表达Netrin-1。用神经元标记Neun进行的共定位研究表明，Netrin-1在多种类型的脊髓中间神经元和运动神经元中表达。识别胶质细胞类型的标记表明，netrin-1在大多数(如果不是全部)少突胶质细胞中表达，但不在星形胶质细胞中表达。在神经发育过程中，netrin-1被认为是轴突生长的可扩散的远程信号。我们发现，在成年脊髓中，大多数Netrin-1蛋白不是自由溶解的，而是与膜或细胞外基质相联系的。对成年脊髓白质的分级显示，在富含致密髓鞘的部分中不存在netrin-1，而在含有轴突周围髓鞘和轴膜的部分中富含netrin-1，这表明netrin-1蛋白可能定位于轴突周围间隙。这些发现表明，除了作为轴突发育的远程指导信号外，netrin可能还具有与细胞表面相关的短期功能，有助于维持成熟神经系统中适当的神经元和轴突-少突胶质细胞之间的相互作用。
Netrins are a family of secreted proteins that function as chemotropic axon guidance cues during neural development. Here we demonstrate that netrin-1 continues to be expressed in the adult rat spinal cord at a level similar to that in the embryonic CNS. In contrast, netrin-3, which is also expressed in the embryonic spinal cord, was not detected in the adult. In situ hybridization analysis demonstrated that cells in the white matter and the gray matter of the adult spinal cord express netrin-1. Colocalization studies using the neuronal marker NeuN revealed that netrin-1 is expressed by multiple classes of spinal interneurons and motoneurons. Markers identifying glial cell types indicated that netrin-1 is expressed by most, if not all, oligodendrocytes but not by astrocytes. During neural development, netrin-1 has been proposed to function as a diffusible long-range cue for growing axons. We show that in the adult spinal cord the majority of netrin-1 protein is not freely soluble but is associated with membranes or the extracellular matrix. Fractionation of adult spinal cord white matter demonstrated that netrin-1 was absent from fractions enriched for compact myelin but was enriched in fractions containing periaxonal myelin and axolemma, indicating that netrin-1 protein may be localized to the periaxonal space. These findings suggest that in addition to its role as a long-range guidance cue for developing axons, netrin may have a short-range function associated with the cell surface that contributes to the maintenance of appropriate neuronal and axon-oligodendroglial interactions in the mature nervous system.