9511013 D'Mello During the development of the vertebrate nervous system, approximately half of the neurons generated die around the time of birth by a process known as programmed cell death (PCD or apoptosis). Although leading to the massive death of neuronal populations, this process is necessary for the normal development of the nervous system. It is now well established that PCD is not restricted to the nervous system, but occurs in virtually all tissue and cell types and represents a fundamental biological process serving to eliminate unwanted or superfluous cells. A question of significant importance is whether the inappropriate activation of the apoptotic program underlies abnormal neuronal loss. The objective of this proposal is to understand the mechanisms controlling PCD in neurons. More specifically, genes that induce or suppress the death process will be identified, A cell culture model system using neurons from the vertebrate cerebellum has previously been developed and will be used to identify genes that regulate neuronal death. In the long term, these investigations will provide fundamental information concerning the processes underlying neuronal death during development.
