Complementary roles of BDNF and NT-3 in vestibular and auditory development.
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 mutants showed 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.
Ernfors
P
P
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA.
Van De Water
T
T
Loring
J
J
Jaenisch
R
R
D000344:Afferent Pathways / Q000166:cytology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D003051:Cochlea / Q000294:innervation; D004525:Efferent Pathways / Q000166:cytology; D006198:Hair Cells, Auditory / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D020933:Neurotrophin 3; D014722:Vestibule, Labyrinth / Q000294:innervation* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3