The zebrafish unplugged gene controls motor axon pathway selection.

En route to their targets, motor axons encounter choice points at which they select their future path. Experimental studies predict that at each choice point specialized cells provide local guidance to pathfinding motor axons, however, the identity of these cells and their signals is unknown. Here, we identify the zebrafish unplugged gene as a key component for choice point navigation of pioneering motor axons. We show that in unplugged mutant embryos, motor neuron growth cones reach the choice point but make inappropriate pathway decisions. Analysis of chimeric embryos demonstrates that unplugged activity is produced by a selective group of mesodermal cells located adjacent to the choice point. As the first motor growth cones approach the choice point, these mesodermal cells migrate away, suggesting that unplugged activity influences growth cones by a contact-independent mechanism. These data suggest that unplugged defines a somite-derived signal that elicits differential guidance decisions in motor growth cones.