A central problem in developmental neurobiology is the understanding of the regulation of neuron survival and death. The neurotrophic theory provides a basis for understanding several features of neuronal development, including the question of why, in many populations of developing neurons, only a proportion of the original number of postmitotic cells survives. It is well known that in many regions of the nervous system large numbers (approx. 50%) of postmitotic neurons degenerate and die by a process of naturally occurring neuronal death. It has been repeatedly demonstrated that in most populations of neurons this normal cell loss occurs during the period when neurons are establishing synaptic connections with their targets. This temporal coincidence, together with the demonstration that manipulations of the availability of putative synaptic targets alters the number of surviving innervating neurons, led to the proposal that neurons compete for a target-derived factor that is supplied in limiting amounts by the targets and thus adjusting neuron numbers so as to provide sufficient innervations for their targets. However, there is growing evidence that other mechanisms may be involved in regulating cell death.
