SEMAPHORIN-III CAN REPULSE AND INHIBIT ADULT SENSORY AFFERENTS IN-VIVO

During development, semaphorins (collapsin, fasciclin) mediate repulsi ve and inhibitory guidance of neurons(1-4). Semaphorin III, a secretab le member of this family, is expressed by the ventral spinal cord at t he time corresponding to projection of sensory afferents from the dors al root ganglion (DRG) into the spinal cord(6). The inhibitory effect of E14 ventral cord is active only on nerve growth factor (NGF)-respon sive sensory afferents (small-diameter A-delta and C fibers subserving sensations of temperature and pain)(5). Similarly, COS cells secretin g recombinant semaphorin III are able to selectively repel DRG afferen ts whose growth is stimulated by NGF and not NT-3 (ref. 7). However, i t is not known whether these molecules can exert a functional role in the fully developed adult peripheral nervous system. In this study, we demonstrated that gene gun transfection and production of semaphorin III in corneal epithelial cells in adult rabbits in vivo can cause rep ulsion of established A-delta and C fiber trigeminal sensory afferents . In addition, it is shown that, following epithelial wounding and den ervation, semaphorin III is able to inhibit collateral nerve sprouts f rom innervating the reepithelialized tissue. These findings are signif icant in that they provide direct evidence that small-diameter adult s ensory neurons retain the ability to respond to semaphorin III. In add ition, the corneal gene gun technique may be generally used to study t he in vivo effects of neural growth modulators by quantifying the amou nt of sensory nerve growth.