Development and plasticity of commissural circuits: from locomotion to brain repair

•A description of genetic determinants of axonal laterality.•Enhancing axon collateral sprouting across the midline improves brain repair.•Diversity of commissural circuits and their function in locomotion.

Commissural neurons project their axons across the midline of the nervous system to contact neurons on the opposite side. Although their existence has been known for more than a century, the function of brain commissures, as well as their diversity and evolutionary advantage, are far from understood. Recent genetic studies in mammals have led to the identification of subsets of commissural neurons, which, in the hindbrain and spinal cord, control the tuning and bilateral coordination of locomotion. The molecular mechanisms and transcriptional programs which specify axonal laterality during development are also now being elucidated. Finally, new studies have confirmed that axonal laterality is plastic and that facilitating the commissural sprouting of axon collaterals might influence functional recovery after brain injury.