FGF22 signaling regulates synapse formation during post-injury remodeling of the spinal cord
FGF22 signaling regulates synapse formation during post-injury remodeling of the spinal cord
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DOI：
10.15252/embj.201490578
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发表时间：
2015-05-05
期刊：
影响因子：
11.4
通讯作者：
Bareyre, Florence M.
中科院分区：
文献类型：
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作者：
Jacobi, Anne;Loy, Kristina;Bareyre, Florence M.
损伤后轴突回路的重塑需要形成新的突触接触以实现功能恢复。目前还不清楚是哪些分子信号启动了成年中枢神经系统的轴突和突触重组。在这里，我们确定FGF22是受损脊髓回路重塑的关键调节因子。我们发现，FGF22是由脊髓中继神经元，而其主要受体FGFR1和FGFR2的皮质投射神经元表达。在脊髓损伤小鼠模型中，FGF22缺陷或后肢运动皮质中FGFR1和FGFR2的靶向缺失限制了皮质脊髓侧支和中继神经元之间新突触的形成，延迟了它们的分子成熟，并阻碍了功能恢复。这些结果确立了FGF 22作为成人神经系统中的突触发生介质以及脊髓损伤后重塑期间突触形成和成熟的关键调节剂。
The remodeling of axonal circuits after injury requires the formation of new synaptic contacts to enable functional recovery. Which molecular signals initiate such axonal and synaptic reorganisation in the adult central nervous system is currently unknown. Here, we identify FGF22 as a key regulator of circuit remodeling in the injured spinal cord. We show that FGF22 is produced by spinal relay neurons, while its main receptors FGFR1 and FGFR2 are expressed by cortical projection neurons. FGF22 deficiency or the targeted deletion of FGFR1 and FGFR2 in the hindlimb motor cortex limits the formation of new synapses between corticospinal collaterals and relay neurons, delays their molecular maturation, and impedes functional recovery in a mouse model of spinal cord injury. These results establish FGF22 as a synaptogenic mediator in the adult nervous system and a crucial regulator of synapse formation and maturation during post-injury remodeling in the spinal cord.