Axotomy-induced Smad1 activation promotes axonal growth in adult sensory neurons.
Axotomy-induced Smad1 activation promotes axonal growth in adult sensory neurons.
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DOI：
10.1523/jneurosci.5397-08.2009
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发表时间：
2009-06-03
期刊：
影响因子：
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通讯作者：
Tessier-Lavigne M
中科院分区：
文献类型：
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作者：
Zou H;Ho C;Wong K;Tessier-Lavigne M
成熟的神经元具有减弱的内在再生能力。成年人背根神经节（DRG）外周分支的轴突切断术（一种“条件性”损伤）触发转录依赖性轴突生长程序。在这里，我们表明，这种生长程序需要的转录因子Smad1的功能。外周轴突切断后，神经元Smad1上调，磷酸化Smad1在细胞核中积累。这两个事件之前的轴突延伸的发病。通过RNA干扰在体外减少Smad1损害轴突生长，并且需要Smad1的持续存在来维持生长程序。此外，神经节内注射BMP 2或4，激活Smad1，显着增强轴突生长能力，模仿的效果的条件性病变。因此，通过轴突切断激活Smad1是促进成人感觉神经元增强生长状态的转录开关的关键组成部分。
Mature neurons have diminished intrinsic regenerative capacity. Axotomy of the peripheral branch of adult dorsal root ganglia (DRG) (a “conditioning” lesion) triggers a transcription-dependent axon growth program. Here we show that this growth program requires the function of the transcription factor Smad1. Following peripheral axotomy, neuronal Smad1 is up-regulated, and phosphorylated Smad1 accumulates in the nucleus. Both events precede the onset of axonal extension. Reducing Smad1 by RNA interference in vitro impairs axonal growth, and the continued presence of Smad1 is required to maintain the growth program. Furthermore, intraganglionic injection of BMP2 or 4, which activates Smad1, markedly enhances axonal growth capacity, mimicking the effect of a conditioning lesion. Thus, activation of Smad1 by axotomy is a key component of the transcriptional switch that promotes an enhanced growth state of adult sensory neurons.