Trigeminal Ganglion Axons Are Repelled By Their Presumptive Targets

Abstract

Previous work suggested that in mouse, presumptive targets of the trigeminal 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 trigeminal axons. The repellant activity is concentrated in the anterior and ventral epithelium of the mandibular arch at embryonic day 12 (E12) and was also present in the maxillary arch. The activity is blocked by anti-neuropilin-1. E13 mandible explants repel trigeminal axons during the first day of outgrowth in vitro, but thereafter permit or attract trigeminal ganglion axon outgrowth. By E14, lingual nerve afferents first enter the tongue in vivo, and the repellant influence becomes restricted to the midline. The progressive restriction of the repellant influence may contribute to the in vivo progression of nerve development: 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 loss of repellant influence from presumptive lateral tongue surface results from downregulation of the repellant activity, not of responsiveness 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 arrived near the target, intermediate structures must guide these axons initially.

BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development

“…Combined with the in situ hybridisation study for TrkB, our results suggest that the failure of rescue of the gustatory system in BDNF NT3/NT3 mice is, just as in the dorsal root ganglia during target innervation, caused by a temporally selective expression of TrkB in the gustatory neurons that prevent these neurons from responding to NT3 and as a consequence, the neurons fail to survive and innervate the target tissue. The failure of NT3-dependent perigemmal somatosensory nerve fibres to invade the intragemmal territory, which in these mice express NT3, indicates that in addition to neurotrophins stimulating innervation of these territories, other mechanisms participate in preventing innervation of a tissue by a particular class of sensory neurons (Rochlin and Farbman, 1998;Rochlin et al, 2000).…”

The role of neuropilins in cancer

“…NRP-1-and NRP-2-deficient animals exhibit abnormal neural trajectories and inappropriate projection of a number of different classes of neurons (1 -3, 77 -80). These effects are thought to be mediated by defects in axonal repulsion (5,81,82).…”

Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfβ1 regulate semaphorin 3a expression in the dental mesenchyme

“…Experimental and genetic analyses have provided evidence that Npn1 mediates in vivo effects of Sema3a on trigeminal axons during their pathfinding (Kitsukawa et al, 1997;Rochlin and Farbman, 1998). To analyze whether Npn1 is a signaling receptor for Sema3a in dental axons, we first analyzed its mRNA expression in trigeminal sensory ganglion.…”