The autoregulation of retinal ganglion cell number.

The development of the nervous system is dependent on a complex set of signals whose precise co-ordination ensures that the correct number of neurones are generated. This regulation is achieved through a variety of cues that influence both the generation and the maintenance of neurones during development. We show that in the chick embryo, stratified retinal ganglion cells (RGCs) are themselves responsible for providing the signals that control the number of RGCs that are generated, both by inhibiting the generation of new ganglion cells and by killing incoming migratory ganglion cells. Selective toxicological ablation of RGCs in the chick embryo resulted in the achronic generation of ganglion cells, which eventually led to the repopulation of the ganglion cell layer and a large decrease in the physiological cell death affecting postmitotic migratory neurones. Interestingly, the application of exogenous NGF reversed the effects of ganglion cell ablation on ganglion cell death. Because the only source of NGF in the retina is that produced by the stratified ganglion cells, we infer that these differentiated neurones regulate their own cell number by secreting NGF, a neurotrophin that has previously been shown to be responsible for the death of migrating ganglion cells.