NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors

Superior cervical ganglia of postnatal mice with a targeted disruption of t he gene for neurotrophin-3 have 50% fewer neurons than those of wild-type m ice. In culture, neurotrophin-3 increases the survival of proliferating sym pathetic precursors. Both precursor death (W. ElShamy et al., 1996, Develop ment 122, 491-500) and, more recently, neuronal death (S. Wyatt et al., 199 7, EMBO J. 16, 3115-3123) have been described in mice lacking NT-3. Consist ent with the second report, we found that, in vivo, neurogenesis and precur sor survival were unaffected by the absence of neurotrophin-3 but neuronal survival was compromised so that only 50% of the normal number of neurons s urvived to birth. At the time of neuron loss, neurotrophin-3 expression, as sayed with a lacZ reporter, was detected in sympathetic target tissues and blood vessels, including those along which sympathetic axons grow, suggesti ng it may act as a retrograde neurotrophic factor, similar to nerve growth factor. To explore this possibility, we compared neuron loss in neurotrophi n-3-deficient mice with that in nerve growth factor-deficient mice and foun d that neuronal losses occurred at approximately the same time in both muta nts, but were less severe in mice lacking neurotrophin-3. Eliminating one o r both neurotrophin-3 alleles in mice that lack nerve growth factor does no t further reduce sympathetic neuron number in the superior cervical ganglio n at E17.5 but does alter axon outgrowth and decrease salivary gland innerv ation. Taken together these results suggest that neurotrophin-3 is required for survival of some sympathetic neurons that also require nerve growth fa ctor. (C) 1999 Academic Press.