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首页> 外文期刊>Neuron >Sonic hedgehog guides axons through a noncanonical, Src-family-kinase-dependent signaling pathway.
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Sonic hedgehog guides axons through a noncanonical, Src-family-kinase-dependent signaling pathway.

机译：声波刺猬引导轴突通过非经典的Src家族激酶依赖性信号通路。

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摘要

Sonic hedgehog (Shh) plays essential roles in developmental events such as cell fate specification and axon guidance. Shh induces cell fate specification through canonical Shh signaling, mediated by transcription. However, the mechanism by which Shh guides axons is unknown. To study this, we developed an in vitro assay for axon guidance, in which neurons can be imaged while responding to a defined gradient of a chemical cue. Axons of dissociated commissural neurons placed in a Shh gradient turned rapidly toward increasing concentrations of Shh. Consistent with this rapid response, we showed that attraction by Shh does not require transcription. Instead, Shh stimulates the activity of Src family kinase (SFK) members in a Smoothened-dependent manner. Moreover, SFK activity is required for Shh-mediated guidance of commissural axons, but not for induction of Gli transcriptional reporter activity. Together, these results indicate that Shh acts via a rapidly acting, noncanonical signaling pathway to guide axons.
机译：音速刺猬（Shh）在诸如细胞命运规格和轴突指导等发育事件中起着至关重要的作用。 Shh通过规范的Shh信号传导（通过转录介导）诱导细胞命运规范。但是，Shh引导轴突的机制尚不清楚。为了研究这一点，我们开发了一种针对轴突引导的体外测定方法，该方法可以在对定义的化学提示梯度做出反应的同时对神经元进行成像。放置在Shh梯度中的分离的连合神经元的轴突迅速转向增加的Shh浓度。与这种快速反应一致，我们证明了Shh的吸引力不需要转录。相反，Shh以平滑化依赖性方式刺激Src家族激酶（SFK）成员的活性。此外，SFK活性是Shh介导的连合轴突所需的，而不是诱导Gli转录报告子活性的。总之，这些结果表明，Shh通过快速起作用的非经典信号传导途径起作用来指导轴突。

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