During neuronal development, the formation of neural circuits requires developing axons to traverse a diverse cellular and molecular environment to establish synaptic contacts with the appropriate postsynaptic partners. Essential to this process is the ability of developing axons to navigate guidance molecules presented by specialized populations of cells. These cells partition the distance traveled by growing axons into shorter intervals by serving as intermediate targets, orchestrating the arrival and departure of axons by providing attractive and repulsive guidance cues. The floor plate in the central nervous system (CNS) is a critical intermediate target during neuronal development, required for the extension of commissural axons across the ventral midline. In this review, we begin by giving a historical overview of the ventral commissure and the evolutionary purpose of decussation. We then review the axon guidance studies that have revealed a diverse assortment of midline guidance cues, as well as genetic and molecular regulatory mechanisms required for coordinating the commissural axon response to these cues. Finally, we examine the contribution of dysfunctional axon guidance to neurological diseases
