Subtractive Hybridization: A Method to Identify Novel Genes Induced During Neuronal Programmed Cell Death

Neuronal programmed cell death (PCD) is a well-recognized developmental phenomenon that culminates in apoptosis (reviewed in Oppenheim, 1991). Shortly after the period of neuroblast proliferation, many neurons, commonly about 50%, die during a circumscribed period at about the time functional connections are being made. A primary, but probably not only, purpose for this process appears to be to match the number of innervating neurons to the size of their targets. Target-or locally derived trophic factors typically control neuronal survival during, and subsequent to, this period. In the most widely accepted scenario, trophic factors are secreted in minute amounts by their target, bind to receptors on the innervating nerve terminals, are internalized, and are retrogradely transported to the neuronal cell body. An unidentified, retrogradely transported signal activates mechanisms that maintain the survival of the cell and trigger a variety of trophic responses. Presumably during the period of naturally occurring neuronal death, cells that fail to obtain sufficient trophic factor die, whereas those that obtain sufficient factor survive.