Neurotrophins and other growth factors in the generation of retinal neurons.

The generation of neurons in the vertebrate retina, as in other areas of the developing nervous system, largely depends on extracellular signals. Of the known signaling molecules, neurotrophins play decisive, defined, and distinct roles. The three neurotrophins identified in the chick, namely, neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), are expressed in either the pigment epithelium (NT-3 and BDNF) or in the neural retina (NGF) at the onset of neuron birth. In addition, trkC and trkB, receptors for NT-3 and BDNF, respectively, together with p75, the low-affinity neurotrophin receptor, are expressed in the retina at the same developmental period. The role of these three neurotrophins in the differentiation of neurons in the chick retina has been elucidated by a combination of in vitro and in vivo experiments. Thus, NT-3 promotes the conversion of neuroepithelial cells into neurons, whereas BDNF and NGF control the programmed cell death (apoptosis) that affects early postmitotic neuroblasts. BDNF, acting via its trkB receptor, is a survival factor for these cells, whereas NGF, binding to p75 receptor, acts as a killing factor, thereby controlling the provisional number of newly generated neurons.