MICE LACKING BRAIN-DERIVED NEUROTROPHIC FACTOR DEVELOP WITH SENSORY DEFICITS

DURING vertebrate development, neuronal survival depends on target-derived neurotrophic factors(1,2). Brain-derived neurotrophic factor(3) (BDNF), a member of the neurotrophin family, can prevent the death of particular peripheral sensory neurons in vitro(4-6), and of central motor neurons as well as dopaminergic and cholinergic neurons of the basal forebrain during development(7-9). It also prevents the death of motor neurons and midbrain dopaminergic neurons induced by lesions(8,10-12). Here we show that mutant mice lacking BDNF have severe deficiencies in coordination and balance, associated with excessive degeneration in several sensory ganglia including the vestibular ganglion. The few remaining vestibular axons fail to contact the vestibular sensory epithelia, and terminate in the adjacent connective tissue. Survival of sympathetic, midbrain dopaminergic and motor neurons is not affected. These results indicate that BDNF is required for the survival and target innervation of particular neuronal populations.