In vertebrates, commissural neuron axons grow towards the ventral midline in response to attractive cues. Upon reaching the midline, axons begin to respond to repulsive cues, such as Slit, through cognate Robo receptors. Importantly, axonal sensitivity to Slit increases while they traverse the midline and is maintained after they exit on the other side. The mechanisms responsible for this increased Slit sensitivity are not fully understood. Now, Junichi Yuasa-Kawada and colleagues identify new components in Slit-Robo signalling-mediated guidance of commissural neurons. Using a neuronal culture system, the authors show that stimulation with Slit promotes endocytic recycling of Robo1, which increases Robo1 levels in the axon. Supporting this, they find that Slit-Robo signalling activates ADP-ribosylation factor 6 (Arf6), which is a factor known to play important roles in endocytosis and recycling. The authors demonstrate that commissural axons in Arf6 knockout mice and knockdown explant cultures are desensitised to Slit. Taken together, these data suggest that Arf6 maintains a positive-feedback loop whereby Slit repulsion is enhanced by Arf6-mediated endocytic recycling of Robo1. This study provides new insights into the mechanism for switching the response of commissural axons to various guidance cues at the midline.
Commissural axons stay on the right path with Arf6
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Commissural axons stay on the right path with Arf6. Development 1 February 2019; 146 (3): e0303. doi:
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