TRIGEMINAL GANGLION AXONS ARE REPELLED BY THEIR PRESUMPTIVE TARGETS

Previous work suggested that in mouse, presumptive targets of the trig eminal ganglion, rather than intermediate structures, attract pioneer axons from the time their growth cones exit the ganglion (Lumsden and Davies, 1986). In rat we find that some presumptive targets repel trig eminal axons. The repellant activity is concentrated in the anterior a nd ventral epithelium of the mandibular arch at embryonic day 12 (E12) and was also present in the maxillary arch. The activity is blocked b y anti-neuropilin-1. E13 mandible explants repel trigeminal axons duri ng the first day of outgrowth in vitro, but thereafter permit or attra ct trigeminal ganglion axon outgrowth. By E14, lingual nerve afferents first enter the tongue in vivo, and the repellant influence becomes r estricted to the midline. The progressive restriction of the repellant influence may contribute to the in vivo progression of nerve developm ent: the earliest afferents turn anteriorly lateral to the tongue, but subsequently arriving afferents advance into the tongue and then turn away from the midline. Thus, the repellant may influence the order of nerve branch development and the timing of innervation of epithelial and subepithelial targets. Heterochronic studies revealed that the los s of repellant influence from presumptive lateral tongue surface resul ts from downregulation of the repellant activity, not of responsivenes s to the repellant. Because presumptive targets repel trigeminal axons during the initial stages of advance from the trigeminal ganglion and do not have a net attractive influence until after afferents have arr ived near the target, intermediate structures must guide these axons i nitially.