The morphogen Sonic hedgehog is an axonal chemoattractant that collaborates with Netrin-1 in midline axon guidance
The morphogen Sonic hedgehog is an axonal chemoattractant that collaborates with Netrin-1 in midline axon guidance
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DOI：
10.1016/s0092-8674(03)00199-5
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发表时间：
2003-04-04
期刊：
影响因子：
64.5
通讯作者：
Tessier-Lavigne, M
中科院分区：
文献类型：
--
作者：
Charron, F;Stein, E;Tessier-Lavigne, M
发育中的轴突在吸引性和排斥性导向信号的引导下到达其目标。在胚胎脊髓中，底板趋化因子Netrin - 1是引导连合神经元轴突到达中线所必需的。然而，遗传学证据表明，其他趋化因子也参与其中。我们发现，形态发生素音猬因子（Shh）在体外能够模拟底板的额外趋化活性，并且能够直接作为分离轴突的趋化因子发挥作用。环巴胺介导的对Shh信号传导介质平滑蛋白（Smo）的抑制，或者连合神经元中Smo的条件性失活表明，Smo的活性对于体外底板的额外趋化活性以及体内连合轴突向底板的正常投射是重要的。这些结果提供了证据，表明Shh通过Smo发挥作用，是连合轴突的一种中线来源的趋化因子，并且表明一种形态发生素也可以作为一种轴突趋化因子发挥作用。
Developing axons are guided to their targets by attractive and repulsive guidance cues. In the embryonic spinal cord, the floor plate chemoattractant Netrin-1 is required to guide commissural neuron axons to the midline. However, genetic evidence suggests that other chemoattractant(s) are also involved. We show that the morphogen Sonic hedgehog (Shh) can mimic the additional chemoattractant activity of the floor plate in vitro and can act directly as a chemoattractant on isolated axons. Cyclopamine-mediated inhibition of the Shh signaling mediator Smoothened (Smo) or conditional inactivation of Smo in commissural neurons indicate that Smo activity is important for the additional chemoattractant activity of the floor plate in vitro and for the normal projection of commissural axons to the floor plate in vivo. These results provide evidence that Shh, acting via Smo, is a midline-derived chemoattractant for commissural axons and show that a morphogen can also act as an axonal chemoattractant.