Proliferation, differentiation, and survival of rat sensory neuron precursors in vitro require specific trophic factors.

To determine critical periods of action, the effects of trophic factors on rat lumbar dorsal root ganglion (DRG) neurons were evaluated during neurogenesis, and after neurogenesis, before and after target contact. Brain-derived neurotrophic factor and neurotrophin-4 increased E12.5 DRG neuronal survival. Leukemia inhibitory factor enhanced neuronal differentiation. NGF and NT3 increased BrdU incorporation in neurons derived from E12.5 DRG neuroblasts. By contrasts, neurotrophin dependence switched at E14.5 such that BDNF had no survival activity but NGF, NT3, and NT4 supported survival of the same neurons. At birth, DRG neurons were supported by NGF and to a lesser extent, leukemia inhibitory factor. Thus, specific trophic factors discretely regulate proliferation, differentiation, and survival in DRG at different ages. This study complements genetic studies of neurotrophin and trk activity by identifying the critical period of action for and the specific events regulated by each neurotrophin.