Regulated formation and selection of neuronal processes underlie directional guidance of neuronal migration

Abstract

Axon guidance and neuronal migration are critical features of neural development, and it is believed that extracellular gradients of secreted guidance cues play important roles in pathfinding. It has been well documented that the growth cones of extending axons respond to such extracellular gradients by growing toward or away from the source of the secreted cue via asymmetrical extension of a single growth cone. However, it is unclear whether migrating neurons change direction in response to guidance molecules using the same mode of turning as extending axons. In this study, we demonstrate that migrating neurons turn away from the chemorepellent Slit through repeated rounds of process extension and retraction and do not turn through the reorientation of a single growth cone. We further show that Slit increases the rate of somal process formation and that these processes form preferentially on the side of the cell body furthest away from the Slit source. In addition, Slit causes cell turning through asymmetric process selection. Finally, we show that multiple types of migrating neurons employ this mode of cell turning in response to a variety of guidance cues. These results show that migrating neurons employ a unique type of turning when faced with secreted guidance cues that is distinct from the type employed by axons.