| Summary: | The centrally projecting sensory axons of the dorsal root ganglia follow a well established pattern that is conserved across many species and offers a robust model for the study of axonal guidance. When primary sensory axons leave the sensory ganglia and project to the embryonic spinal cord, they do not immediately extend into the spinal cord dorsal horn, but bifurcate and travel long the rostrocaudal axis of the animal to form the dorsal funiculus and Lissaur’s tract. At a later stage they extend collateral fibres that enter the dorsal horn and target to specific laminae according to their sensory modality. The factors that prevent immediate entry into the dorsal horn or regulate the timing of sensory collateral formation and specificity of lamina innervation have not been clearly identified. Our lab previously showed that Semaphorin5B (Sema5B), a member of the semaphorin family of guidance molecules, is dynamically expressed in the embryonic spinal cord and correlates with these sensory axon targeting events. Using in vitro assays, I show systematically that Sema5B inhibits growth of both nerve growth factor-responsive and neurotrophin-3-responsive dorsal root ganglion neurites and that this inhibitory effect on the former is mediated in part through the cell adhesion molecule TAG-1. Using the technique of RNA interference, I show in vivo that a reduction-of-function of Sema5B in the spinal cord leads to cutaneous axons not only projecting prematurely into, but to erroneous targets within the dorsal horn of the spinal cord, while proprioceptive axons continued to pathfind correctly. Together, these results suggest that Sema5B acts as a repulsive barrier for centrally projecting primary sensory axons that first reach the spinal cord, and once collaterals form, Sema5B exerts a differential function on different types of sensory fibres to regulate their pathfinding. This is the first study to identify the specific cue that regulates sensory neuron entry and guidance into the spinal cord dorsal horn grey matter.
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