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 factor s on rat lumbar dorsal root ganglion (DRG) neurons were evaluated duri ng neurogenesis, and after neurogenesis, before and after target conta ct. 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 contrast, neurotrophin dependen ce 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 neu rons were supported by NGF and to a lesser extent, leukemia inhibitory factor. Thus, specific trophic factors discretely regulate proliferat ion, differentiation, and survival in DRG at different ages. This stud y complements genetic studies of neurotrophin and trk activity by iden tifying the critical period of action for and the specific events regu lated by each neurotrophin.