Developing vestibular ganglion neurons switch trophic sensitivity from BDNF to GDNF after target innervation

Recent evidence showing a distinctive cell loss in vestibular and cochlear ganglia of brain-derived neurotrophic factor (BDNF) versus neurotrophin-3 ( NT-3) null mutant mice demonstrates that these neurotrophins play a critica l role in inner ear development. In this study, biological functions of BDN F and NT-3 in the chick vestibular and cochlear ganglion development was as sessed in vitro and compared to those of other neurotrophic factors. The em bryonic day (E)8-12 vestibular ganglion neurons showed an extensive outgrow th in response to BDNF with less outgrowth to NT-3, In contrast, NT-3 had s tronger neurotrophic effects on the E12 cochlear ganglion neurons compared to BDNF. These results support previous evidence that neurotrophins play im portant roles in the vestibular and cochlear ganglion neuron development. H owever, the responsiveness to the neurotrophins declined and became undetec table by E16. Unexpectedly, glial cell line-derived neurotrophic factor (GD NF) promoted neurite outgrowth from vestibular ganglia at E12-16, later tha n the stages at which BDNF had neurotrophic effects. The time of switching sensitivity of the vestibular ganglion neurons from BDNF to GDNF correlated with the time of completion of synaptogenesis on their peripheral and cent ral targets, Furthermore, a factor released from E12 inner ears exerted neu rotrophic effects on late-stage vestibular ganglion neurons that were not r esponsive to the E4 otocyst-derived factor. These results raise the possibi lity that the vestibular ganglion neurons become responsive to GDNF upon ta rget innervation and that the changes in sensitivity are regulated by chang es in available factors released from their peripheral targets, the inner e ar epithelia. (C) 1999 John Wiley & Sons, Inc.