McWilliams Thomas G, Howard Laura, Wyatt Sean, Davies Alun M
Division of Molecular Biosciences, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, Wales.
Division of Molecular Biosciences, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, Wales.
Cell Rep. 2015 Mar 10;10(9):1443-1449. doi: 10.1016/j.celrep.2015.02.016. Epub 2015 Mar 5.
The regulation of innervation by target-derived factors like nerve growth factor (NGF) is the cornerstone of neurotrophic theory. Whereas autocrine signaling in neurons affecting survival and axon growth has been described, it is difficult to reconcile autocrine signaling with the idea that targets control their innervation. Here, we report that an autocrine signaling loop in developing mouse sympathetic neurons involving CD40L (TNFSF5) and CD40 (TNFRSF5) selectively enhances NGF-promoted axon growth and branching, but not survival, via CD40L reverse signaling. Because NGF negatively regulates CD40L and CD40 expression, this signaling loop operates only in neurons exposed to low levels of NGF. Consequently, the sympathetic innervation density of tissues expressing low NGF is significantly reduced in CD40-deficient mice, whereas the innervation density of tissues expressing high levels of NGF is unaffected. Our findings reveal how differential regulation of autocrine signaling in neurons has region-specific effects on axon growth and tissue innervation.
由神经生长因子（NGF）等靶源性因子对神经支配的调节是神经营养理论的基石。虽然已经描述了神经元中影响存活和轴突生长的自分泌信号传导，但自分泌信号传导与靶标控制其神经支配的观点难以协调。在这里，我们报告在发育中的小鼠交感神经元中，涉及CD40L（TNFSF5）和CD40（TNFRSF5）的自分泌信号传导回路通过CD40L反向信号传导选择性地增强NGF促进的轴突生长和分支，但不影响存活。由于NGF负调节CD40L和CD40的表达，因此该信号传导回路仅在暴露于低水平NGF的神经元中起作用。因此，在CD40缺陷小鼠中，表达低NGF的组织的交感神经支配密度显著降低，而表达高水平NGF的组织的神经支配密度不受影响。我们的研究结果揭示了神经元中自分泌信号传导的差异调节如何对轴突生长和组织神经支配产生区域特异性影响。
Zotero 插件
