Semaphorin 6A Mediates Sensory Afferent Projection into the Developing Spinal Cord

Abstract

During vertebrate development, sensory axons project from the peripheral nervous system (PNS) into the spinal cord at the dorsolateral margin via the dorsal roots. They then ascend to the brain in separate tracts depending on sensory modality. This segregation of sensory axons is essential for appropriate perception and reflex activity. We show that radial glial cells support the formation of these tracks by forming scaffolds which channel various axon fasciculi through the spinal cord along the rostrocaudal axis. Semaphorins are the largest family of axon guidance cues expressed during central nervous system (CNS) formation. Class 6 semaphorins are found throughout the developing CNS and play vital roles in the guidance of growing axons in the brain, yet their roles in the spinal cord are relatively unknown. We investigated the role of Sema6A and its canonical receptor PlexinA2 during spinal cord development by comparing the organisation of radial glia and axon tracts in WT, Sema6A‐/‐and PlexinA2‐/‐ mice. This study shows that Sema6A is inhibitory to TAG‐1 expressing sensory axons entering the spinal cord from the dorsal roots and is a key regulator of sensory axon growth through the spinal cord during development. This effect is independent of its receptor PlexinA2. Sema6A is expressed on boundary cap cells in the dorsal root ganglion and the phenotype described here suggests that it acts as a barrier between the CNS and the PNS. The axonal growth guidance properties of Sema6A and the radial glial cell scaffold suggest they may be therapeutic targets for axonal regeneration following spinal cord injury.