Roles of neurotrophin-3 during early development of the peripheral nervous system.

The neurotrophins are structurally related proteins regulating cell numbers in the developing vertebrate nervous system. They are necessary survival factors preventing the death of specific neuronal populations. Previous experiments have indicated that the administration of nerve growth factor or of brain-derived neurotrophic factor during the formation of sensory ganglia and of target innervation increases the number of neurons by preventing normally occurring neuronal death. These results support the view that during development, neuronal numbers are adjusted to the size of the target tissue by the release of limiting amounts of neurotrophins. However, increasing the levels of neurotrophin-3 during the formation of sensory ganglia results in a marked decrease in neuronal numbers, possibly as a consequence of premature cessation of sensory neuroblast proliferation. In sympathetic ganglia, the application of neurotrophin-3 during the formation of the sympathetic chain causes cell numbers to increase, a result also observed following the application of nerve growth factor. It thus appears that neurotrophin-3 and nerve growth factor can regulate cell numbers well before the period of target-derived control, and that neurotrophin-3 affects neuronal numbers in sensory and sympathetic ganglia in opposite ways.