Comparison of neurotrophin and repellent sensitivities of early embryonic geniculate and trigeminal axons

Abstract

Geniculate (gustatory) and trigeminal (somatosensory) afferents take different routes to the tongue during rat embryonic development. To learn more about the mechanisms controlling neurite outgrowth and axon guidance, we are studying the roles of diffusible factors. We previously profiled the in vitro sensitivity of trigeminal axons to neurotrophins and target-derived diffusible factors and now report on these properties for geniculate axons. GDNF, BDNF, and NT-4, but not NT-3 or NGF, stimulate geniculate axon outgrowth during the ages investigated, embryonic days 12-14. Sensitivity to effective neurotrophins is developmentally regulated and different from that of the trigeminal ganglion. In vitro coculture studies revealed that geniculate axons were repelled by branchial arch explants that were previously shown to be repellent to trigeminal axons (Rochlin and Farbman [1998] J Neurosci 18:6840-6852). In addition, some branchial arch explants and untransfected COS7 cells repelled geniculate but not trigeminal axons. Sema3A, a ligand for neuropilin-1, is effective in repelling geniculate and trigeminal axons, and antineuropilin-1, but not antineuropilin-2, completely blocks the repulsion by arch explants that repel axon outgrowth from both ganglia. Sema3A mRNA is concentrated in branchial arch epithelium at the appropriate time to mediate the repulsion. In Sema3A knockout mice, geniculate and trigeminal afferents explore medial regions of the immature tongue and surrounding territories not explored in heterozygotes, supporting our previous hypothesis that Sema3A-based repulsion mediates the early restriction of sensory afferents away from midline structures.

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).…”

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 neurotrophin receptors in taste development.

“…However, in the taste system, although any of these guidance molecules may regulate axon guidance of geniculate neurons, most of them remain un-investigated except semaphorin 3A (Sema3A). Sema3A is expressed in the tongue and required for both trigeminal and geniculate axon guidance ( [62], [54], [63] [68], [69], [70]). …”

“…These results suggest that initial formation of fungiform papillae is nerveindependent, while the maintenance of papillae is nerve-dependent. [74], [75], [54], [76], [50], [56]). Specifically, BDNF is expressed in fungiform papillae before they are innervated ( [73], [74], [75], and has been shown to attract chorda tympani nerves outgrowth in vitro ( [54]).…”

“…Sema3A is expressed in tongue epithelium as early as E13.5 and continues to at least E18.5, and is evident in those fungiform papillae that are penetrated by taste nerves ( [64]). Sema3A repels geniculate ganglion axons in vitro, and Sema3A mutant mice showed increased taste innervation to the middle line of the tongue [54]. In addition, these repellent effects of Sema3A were neurotrophin dependent, both BDNF and NT-4 stimulated taste nerve outgrowth were repelled by Sema3A during development ( [63]).…”