B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS.

B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS.
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DOI:
10.1084/jem.20131780
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发表时间:
2014-05-05
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Zhong J
Zhong J
中科院分区:
其他
文献类型:
--
作者:
O'Donovan KJ;Ma K;Guo H;Wang C;Sun F;Han SB;Kim H;Wong JK;Charron J;Zou H;Son YJ;He Z;Zhong J

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神经元内B-RAF激酶的激活足以驱动外周轴突突起的生长,并使受损视神经的轴突再生生长强劲。激活促进发育性轴突生长的内在生长程序也可能促进受损成年神经元的轴突再生。在这里,我们证明了在没有上游神经营养因子信号的情况下,小鼠胚胎神经元中B-RAF激酶的条件激活足以在体内驱动远程外周感觉轴突的生长。我们进一步表明,激活的B-RAF信号能够在脊髓背根挤压后使感觉轴突强劲地再生生长,并在挤压损伤的视神经中使轴突大量再生。最后,B-RAF功能获得和PTEN功能丧失的结合促进了视神经轴突的延伸,超出了简单相加效应的预测。我们得出的结论是,细胞内禀RAF信号是促进外周和中枢神经系统轴突发育和再生生长的重要途径。
Intraneuronal activation of B-RAF kinase is sufficient to drive the growth of peripheral axon projections and enables robust regenerative axon growth in the injured optic nerve. Activation of intrinsic growth programs that promote developmental axon growth may also facilitate axon regeneration in injured adult neurons. Here, we demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic neurons is sufficient to drive the growth of long-range peripheral sensory axon projections in vivo in the absence of upstream neurotrophin signaling. We further show that activated B-RAF signaling enables robust regenerative growth of sensory axons into the spinal cord after a dorsal root crush as well as substantial axon regrowth in the crush-lesioned optic nerve. Finally, the combination of B-RAF gain-of-function and PTEN loss-of-function promotes optic nerve axon extension beyond what would be predicted for a simple additive effect. We conclude that cell-intrinsic RAF signaling is a crucial pathway promoting developmental and regenerative axon growth in the peripheral and central nervous systems.
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