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.

Gustatory papillae and taste bud development and maintenance in the absence of TrkB ligands BDNF and NT-4

“…Gustatory ganglia express the receptors (trkB and p75 NGFR) for BDNF (Ernfors et al 1992;Nosrat 1998). Previous studies have shown that neurite outgrowth from geniculate ganglion requires BDNF and/or NT-4 (Rochlin et al 2000). We have generated BDNF −/− xNT-4 −/− doubleknockout mice by crossbreeding single neurotrophin knockout mice in order to study the development of the peripheral gustatory system in the absence of TrkB ligands.…”

“…Other candidates are glial cell-line-derived neurotrophic factor (GDNF) and neurturin found in the papillae and in the innervation of the gustatory papillae in the developing tongue (Nosrat 1998;Takeda et al 2004). GDNF has been shown to elicit extensive neurite outgrowth from the geniculate ganglion (Rochlin et al 2000). These other neurotrophic factors may support lingual somatosensory and gustatory innervation in the absence of the neurotrophins BDNF and NT-4.…”

“…In addition, a 40% loss of trigeminal neurons has been recorded in BDNF null mice (Ernfors et al 1994), no loss in NT-4 null mice, and a 30%-34% loss in BDNFxNT-4 double-knockout mice (Liu et al 1995;Conover et al 1995). Moreover neurons in both the geniculate and trigeminal ganglia require BDNF and/or NT-4 for neurite outgrowth (Rochlin et al 2000).…”

Role of neurotrophin in the taste system following gustatory nerve injury

“…Moreover, when knocking out TrkB, 95 % of geniculate ganglion neurons were (Fritzsch et al 1997). In addition to regulating the geniculate neuron number, BDNF and NT-4 differentially regulate neurite outgrowth (Rochlin et al 2000), target innervation, and taste bud development. BDNF produced in taste epithelium is required for gustatory target innervation but NT-4 is not (Hoshino et al 2010;Ma et al 2009).…”

The effect of β-bungarotoxin, or geniculate ganglion lesion on taste bud development in the chick embryo

“…Neuronal growth factor, BDNF significantly increases regenerative neuritic robustness of outgrowth and length in cultured E12-E14 geniculate ganglion cells of rat (Rochlin et al 2000;Yamout et al 2005). Also, BDNF receptor, TrkB mRNA and protein are present in embryonic and young adult geniculate ganglion cells of rodents (e.g., Yamout et al 2005).…”