Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord.

Distinct classes of primary sensory neurons in dorsal root ganglia subserve different sensory modalities, terminate in different dorsoventral locations in the spinal cord, and display different neurotrophin response profiles. Large diameter muscle afferents that terminate in the ventral spinal cord are NT-3 responsive, whereas small diameter afferents subserving pain and temperature are NGF responsive and terminate in the dorsal spinal cord. Previous in vitro studies showed that the developing ventral spinal cord secretes a diffusible factor that inhibits the growth of sensory axons. Here we show that this factor repels NGF-responsive axons but has little effect on NT-3-responsive axons. We also provide evidence implicating semaphorin III/collapsin, a diffusible guidance molecule expressed by ventral spinal cord cells, in mediating this effect. These results suggest that semaphorin III functions to pattern sensory projections by selectively repelling axons that normally terminate dorsally.