Building Spinal and Brain Commissures: Axon Guidance at the Midline

Commissural circuits are brain and spinal cord connections which interconnect the two sides of the central nervous system (CNS). They play essential roles in brain and spinal cord processing, ensuring left-right coordination and synchronization of information and commands. During the formation of neuronal circuits, all commissural neurons of the central nervous system must accomplish a common task, which is to project their axon onto the other side of the nervous system, across the midline that delineates the two halves of the CNS. How this task is accomplished has been the topic of extensive studies over the last past 20 years and remains one of the best models to investigate axon guidance mechanisms. In the first part of this review, I will introduce the commissural circuits, their general role in the physiology of the nervous system, and their recognized or suspected pathogenic properties in human diseases. In the second part of the review, I will concentrate on two commissural circuits, the spinal commissures and the corpus callosum, to detail the cellular and molecular mechanisms governing their formation, mostly during their navigation at the midline.