ROLE OF NEUROTROPHINS IN THE CONTROL OF NEURAL DEVELOPMENT - NEUROTROPHIN-3 PROMOTES BOTH NEURON DIFFERENTIATION AND SURVIVAL OF CULTURED CHICK RETINAL CELLS

The effects of neurotrophins brain-derived neurotrophic factor and neu rotrophin-3 on cultured dissociated cells from chick retina were studi ed at several embryonic ages from day 4 to day 13. Precursor cells fro m days 4-7 retinas proliferated in vitro and, after 20 h in culture, a proportion of them underwent spontaneous differentiation, as judged b y both [H-3]thymidine uptake and acquisition of neuronal morphology an d neuron-specific markers. Brain-derived neurotrophic factor did not a ffect neuronal differentiation, although this factor supports survival of differentiated retinal ganglion cells [Rodriguez-Tebar er al. (198 9) Devl Biol. 136, 296-303]. However, in cultures from young undiffere ntiated retinas, neurotrophin-3 produced up to a 2.5-fold increase in the number of [(3)Hthymidine-positive neurons, i.e. those that in vitr o replicated their DNA. Moreover, in older retinas, neurotrophin-3, li ke brain-derived neurotrophic factor, supported the survival of differ entiated retinal ganglion cells over a short developmental period. Thi s effect was negligible at embryonic day 5, maximal at day 9, decrease d at day 11 and was absent at embryonic day 13. Neurotrophin-3 also su pported the survival of a population of amacrine neurons. This effect was modest at embryonic day 9, and increased at days 11 and 13. Our re sults show that, whereas the action of brain-derived neurotrophic fact or is restricted to differentiated neurons, neurotrophin-3 exerts two distinct successive actions on retinal cells in vitro : first, this fa ctor promotes either differentiation of neuroepithelial cells or matur ation of recently differentiated neurons, and later in development, th is factor supports the survival of differentiated retinal ganglion and amacrine cells but only during a discrete post-differentiation period .