Spatiotemporal clustering of cell death in the avian forebrain proliferative zone.

The extent to which programmed cell death is the fate of proliferative, rather than post-mitotic, cells remains controversial, but a preponderance of evidence suggests that at least some cells within the brain's proliferative zone die during mammalian brain development. One major unresolved question is the extent to which cell death in the proliferative zone is spatiotemporally patterned. In order to answer this question we used the terminal dUTP nick end labeling (TUNEL) method to stain apoptotic cells in the forebrain of chicken embryos at relatively early stages of brain development (Hamburger-Hamilton stages 19-32). Our principal finding is that most of the TUNEL-positive cells within the brain's proliferative zone are concentrated into distinct clusters, whose location varies with developmental stage. At stage 19, many TUNEL+ cells are found within the basal synencephalon, just below where the forebrain's first neurons are located. At stages 24-26, numerous TUNEL+ cells are located within the preoptic area and along the optic stalk. After stage 26, TUNEL labeling is prominent in two telencephalic areas: the thin dorsomedial telencephalon and the thickest portions of the telencephalon's lateral walls (i.e. the dorsal ventricular ridge). Collectively, the observed pattern of TUNEL staining suggests that cell death in the proliferative zone plays a substantial role in shaping the forebrain. In addition, cell death in the proliferative zone may be related to cell cycle exit.