Programmed Cell Death in Neuronal Development

Programmed cell death, or apoptosis, accompanies the development of many tissues, including the vertebrate nervous system. Most neurons are eliminated soon after synaptic contacts have been made between the neurons and their targets. This inspired the neurotrophic theory, which proposes that neurons compete for limited quantities of target-derived survival factors (1–3). Work on nerve growth factor (NGF) in the peripheral nervous system (PNS) (4) gave strong support for this theory: Not only is NGF essential for the survival of specific populations of neurons, but it is also localized in tissues innervated by NGF-responsive neurons in amounts that parallel the density of innervation (5). However, the finding by Southwell et al. (6) that programmed cell death in a major population of neurons in the central nervous system (CNS) is caused by an intrinsic program independent of external cues cannot be readily accommodated by the neurotrophic theory.