Old friends, new story: The role of Slit2C signaling through PlexinA1.

Growth cone guidance is driven by attractive and repulsive signaling cues. Until recently, repulsive signaling by semaphorins was thought to be mediated through Plexin receptors, whereas Slits-induced repulsion was solely mediated through Robo receptors. In a recent report published in Nature Neuroscience, Celine Delloye-Bourgeois and colleagues (2015) combined phenotypic analyses of transgenic mouse lines and in vitro biochemical experiments to identify PlexinA1 as a novel receptor for Slits. Strikingly, they uncovered for the very first time that the Slit2C-terminal fragment possesses some unique biological activity as binding partner for PlexinA1. Even more excitingly, the signaling cascade triggered by SlitC binding to PlexinA1 mediates growth cone collapse of commissural axons both in vivo and ex vivo and nicely complements Robo-Slit signaling in the developing spinal cord midline to prevent midline recrossing.