Vertebrate spinal commissural neurons: a model system for studying axon guidance beyond the midline

For bilaterally symmetric organisms, the transfer of information between the left and right side of the nervous system is mediated by commissures formed by neurons that project their axons across the body midline to the contralateral side of the central nervous system (CNS). After crossing the midline, many of these axons must travel long distances to reach their targets, including those that extend from spinal commissural neurons. Owing to the highly stereotyped trajectories of spinal commissural neurons that can be divided into several segments as these axons project to their targets, it is an ideal system for investigators to ask fundamental questions related to mechanisms of short- and long-range axon guidance, fasciculation, and choice point decisions at the midline intermediate target. In addition, studies of patterning genes of the nervous system have revealed complex transcription factor codes that function in a combinatorial fashion to specify individual classes of spinal neurons including commissural neurons. Despite these advances and the functional importance of spinal commissural neurons in mediating the transfer of external sensory information from the peripheral nervous system (PNS) to the CNS, only a handful of studies have begun to elucidate the mechanistic logic underlying their long-range pathfinding and the characterization of their synaptic targets. Using in vitro assays, in vivo labeling methodologies, in combination with both loss- and gain-of-function experiments, several studies have revealed that the molecular mechanisms of long-range spinal commissural axon pathfinding involve an interplay between classical axon guidance cues, morphogens and cell adhesion molecules. For further resources related to this article, please visit the WIREs website.