PROGRAMMED CELL-DEATH IN THE DEVELOPING NERVOUS-SYSTEM

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.