Charron Frédéric, Stein Elke, Jeong Juhee, McMahon Andrew P, Tessier-Lavigne Marc
Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Cell. 2003 Apr 4;113(1):11-23. doi: 10.1016/s0092-8674(03)00199-5.
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.
发育中的轴突通过吸引性和排斥性导向线索被引导至其靶标。在胚胎脊髓中，底板化学引诱剂Netrin-1是引导连合神经元轴突至中线所必需的。然而，遗传学证据表明其他化学引诱剂也参与其中。我们发现形态发生素音猬因子（Shh）在体外可模拟底板的额外化学引诱活性，并能直接作为分离轴突上的化学引诱剂发挥作用。环杷明介导的对Shh信号传导介质平滑蛋白（Smo）的抑制或连合神经元中Smo的条件性失活表明，Smo活性对于体外底板的额外化学引诱活性以及体内连合轴突向底板的正常投射很重要。这些结果提供了证据，表明Shh通过Smo发挥作用，是连合轴突的一种源自中线的化学引诱剂，并表明一种形态发生素也可作为轴突化学引诱剂。
