Virtually all cell populations in the vertebrate nervous system underg
o massive ''naturally-occurring'' or ''programmed'' cell death (PCD) e
arly in development. Initially neurons and glia are over-produced foll
owed by the demise of approximately one-half of the original cell popu
lation. In this review we highlight current hypotheses regarding how l
arge-scale PCD contributes to the construction of the developing nervo
us system. More germane to the theme of this symposium, we emphasize t
hat the survival of cells during PCD depends critically on their abili
ty to access ''trophic'' molecular signals derived primarily from inte
ractions with other cells. Here we review the cell-cell interactions a
nd molecular mechanisms that control neuronal and glial cell survival
during PCD, and how the inability of such signals to suppress PCD may
contribute to cell death in some diseases such as spinal muscular atro
phy. Finally, by using neurotrophic factors (e.g. CNTF, GDNF) and gene
s that control the cell death cascade (e.g. Bcl-2) as examples, we und
erscore the importance of studying the mechanisms that control neurona
l and glial cell survival during normal development as a means of iden
tifying molecules that prevent pathology-induced cell death. Ultimatel
y this line of investigation could reveal effective strategies for arr
esting neuronal and glial cell death induced by injury, disease, and/o
r aging in humans.