Department of Biological Sciences, Rutgers University, Boyden 206, 195 University Ave,, Newark, NJ 07102, USA.
Neural Dev. 2013 Jul 31;8:15. doi: 10.1186/1749-8104-8-15.
Spinal commissural axons represent a model system for deciphering the molecular logic that regulates the guidance of midline-crossing axons in the developing central nervous system (CNS). Whether the same or specific sets of guidance signals control the navigation of molecularly distinct subtypes of these axons remains an open and largely unexplored question. Although it is well established that post-crossing commissural axons alter their responsiveness to midline-associated guidance cues, our understanding of the repulsive mechanisms that drive the post-crossing segments of these axons away from the midline and whether the underlying guidance systems operate in a commissural axon subtype-specific manner, remains fragmentary at best.
Here, we utilize axonally targeted transgenic reporter mice to visualize genetically distinct dorsal interneuron (dI)1 and dI4 commissural axons and show that the repulsive class 3 semaphorin (Sema3) guidance receptor Neuropilin 2 (Npn2), is selectively expressed on the dI1 population and is required for the guidance of post-crossing dI1, but not dI4, axons. Consistent with these observations, the midline-associated Npn2 ligands, Sema3F and Sema3B, promote the collapse of dI1, but not dI4, axon-associated growth cones in vitro. We also identify, for the first time, a discrete GABAergic population of ventral commissural neurons/axons in the embryonic mouse spinal cord that expresses Npn2, and show that Npn2 is required for the proper guidance of their post-crossing axons.
Together, our findings indicate that Npn2 is selectively expressed in distinct populations of commissural neurons in both the dorsal and ventral spinal cord, and suggest that Sema3-Npn2 signaling regulates the guidance of post-crossing commissural axons in a population-specific manner.
脊髓连合轴突代表了一个用于破译调节发育中中枢神经系统（CNS）中线交叉轴突导向的分子逻辑的模型系统。相同或特定的一组导向信号是否控制这些轴突分子上不同亚型的导航仍然是一个悬而未决的、尚未得到充分探索的问题。尽管已经证实，交叉后的连合轴突改变了它们对中线相关导向线索的反应性，但是我们对于驱动这些轴突交叉后段远离中线的排斥机制的理解，以及潜在的导向系统是否以连合轴突亚型特异性的方式运作，仍然是支离破碎的。
在这里，我们利用轴突靶向的转基因报告小鼠来可视化遗传上不同的背侧中间神经元（dI）1 和 dI4 连合轴突，并表明排斥性 III 类神经丝蛋白（Sema3）导向受体神经纤毛蛋白 2（Npn2）选择性地表达在 dI1 群体上，并需要指导交叉后的 dI1 轴突，但不需要 dI4 轴突。与这些观察结果一致，中线相关的 Npn2 配体 Sema3F 和 Sema3B 在体外促进 dI1 轴突相关生长锥的崩溃，但不促进 dI4 轴突的崩溃。我们还首次在胚胎小鼠脊髓中鉴定出一个表达 Npn2 的离散 GABA 能腹侧连合神经元/轴突群体，并表明 Npn2 是其交叉后轴突正确导向所必需的。
总的来说，我们的研究结果表明，Npn2 选择性地表达在背侧和腹侧脊髓中的连合神经元的不同群体中，并表明 Sema3-Npn2 信号以群体特异性的方式调节交叉后的连合轴突的导向。
