Semaphorin signaling: molecular switches at the midline

To establish axonal connections growth cones must navigate multiple intermediate targets before reaching their final target. During this journey growth cones are guided by extracellular repulsive and attractive signals. Although initially identified as repulsive molecules, members of the semaphorin family include both attractants and repellents. How a navigating growth cone responds to a specific semaphorin is not absolute but instead depends on the biological context in which this cue is encountered. Here we review recent breakthroughs in our understanding of the extrinsic signals and molecular processes that control growth cone responses to class 3 semaphorins (Sema3s) at a well-characterized intermediate target, the spinal cord midline.