WIDESPREAD PROGRAMMED CELL-DEATH IN PROLIFERATIVE AND POSTMITOTIC REGIONS OF THE FETAL CEREBRAL-CORTEX

A key event in the development of the mammalian cerebral cortex is the generation of neuronal populations during embryonic life, Previous st udies have revealed many details of cortical neuron development includ ing cell birthdates, migration patterns and lineage relationships, Pro grammed cell death is a potentially important mechanism that could alt er the numbers and types of developing cortical cells during these ear ly embryonic phases, While programmed cell death has been documented i n other parts of the embryonic central nervous system, its operation h as not been previously reported in the embryonic cortex because of the lack of cell death markers and the difficulty in following the entire population of cortical cells, Here, we have investigated the spatial and temporal distribution of dying cells in the embryonic cortex using an in situ end-labelling technique called 'ISEL+' that identifies fra gmented nuclear DNA in dying cells with increased sensitivity, The per iod encompassing murine cerebral cortical neurogenesis was examined, f rom embryonic days 10 through 18, Dying cells were rare at embryonic d ay 10, but by embryonic day 14, 70% of cortical cells were found to be dying, This number declined to 50% by embryonic day 18, and few dying cells were observed in the adult cerebral cortex. Surprisingly, while dying cells were observed throughout the cerebral cortical wall, the majority were found within zones of cell proliferation rather than in regions of postmitotic neurons. These observations suggest that multip le mechanisms may regulate programmed cell death in the developing cor tex, Moreover, embryonic cell death could be an important factor enabl ing the selection of appropriate cortical cells before they complete t heir differentiation in postnatal life.