The physiological role of BDNF and NT-3 in the development of the vestibular and auditory systems was investigated in mice that carry a deleted BDNF and/or NT-3 gene. BDNF was the major survival factor for vestibular ganglion neurons, and NT-3, for spiral ganglion neurons. Lack of BDNF and NT-3 did not affect ingrowth of nerve fibers into the vestibular epithelium, but BDNF mutants failed to maintain afferent and efferent innervation. In the cochlea, BDNF mutants lost type 2 spiral neurons, causing an absence of outer hair cell innervation. NT-3 mutantsshowed a paucity of afferents and lost 87% of spiral neurons, presumably corresponding to type 1 neurons, which innervate inner hair cells. Double mutants had an additive loss, lacking all vestibular and spiral neurons. These results show that BDNF and NT-3 are crucial for inner ear development and, although largely coexpressed, have distinct and nonoverlapping roles in the vestibular and auditory systems.
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