Building Spinal and Brain Commissures: Axon Guidance at the Midline

Abstract

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.

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Commissural axon navigation: Control of midline crossing in the vertebrate spinal cord by the semaphorin 3B signaling

“…In bilateral organisms, multiple reciprocal neuronal projections interconnect the 2 halves of the central nervous system (CNS), forming a dense network of commissures that allow integration and coordination of left-right neuronal activities 9,36 . During embryonic and early postnatal developmental periods, commissural axons navigate through the central midline at all axial levels, crossing from one side of the CNS to the other one at specific time points and positions 9 .…”

“…During embryonic and early postnatal developmental periods, commissural axons navigate through the central midline at all axial levels, crossing from one side of the CNS to the other one at specific time points and positions 9 . Commissural axons can be surrounded by or mixed with ipsilateral axons that are committed to build circuits between neurons of the same side, and that never cross the midline.…”

“…Specialized groups of local cells lying at the CNS midline are instrumental in segregating the ipsilateral and contralateral axon populations, allowing only the latter to cross the midline (Evans and Bashaw, 2009 9,36 ). In the developing spinal cord, midline crossing takes place ventrally through the floor plate (FP), a crucial patterning center composed of glial cells, which contribute to the specification of the neuronal lineages of the neural tube and adjacent territories by secreting the morphogen SHH 17,24 .…”