A TRANSIENT PHASE OF CELL-DEATH IN THE DEVELOPING MEDIAL FOREBRAIN OFTHE PERINATAL FERRET

A transient bilateral population of cells immediately rostral to the f erret corpus callosum was examined at weekly intervals between embryon ic day 28 and postnatal day 7. This region is tentatively identified a s the medial forebrain apoptosis zone (MFAZ) because of the specific n ature of cell death, and the limited area or zone in which it was obse rved. No other region within the brain or retina exhibited a similar p attern or amount of cell death. Only scattered apoptotic cells were fo und throughout the remainder of the brain - including the cerebral cor tical plate? subplate, and white matter - with the exception of the ve ntricular zone of the lateral ventricles which contained a significant population of apoptotic cells. This study addressed three questions a bout apoptosis in the MFAZ: (1) does apoptotic cell death in this regi on signal the appearance of phagocytic macrophages, (2) does cell dege neration and phagocytosis in this region lead to the formation of an e xtracellular space analogous to the cavum septi pellucidi of rodents, and (3) what is the duration of degeneration, or clearance rate, of ce ll death in this defined region. The MFAZ was first found to contain a poptotic nuclei and macrophages late in gestation, at E34. Numbers of apoptotic nuclei and macrophages peaked one week later at birth in thi s area, but disappeared early in postnatal life. During this period, f ormation of a space rostral to the corpus callosum due to the removal of apoptotic cells was not observed. Finally, presence of apoptotic ce lls in the MFAZ over a period of greater than or equal to 9 days sugge sts a clearance rate of many hours. The close spatiotemporal correlati on of the distribution of apoptotic cells and their removal by macroph ages suggests that these are interrelated, and perhaps interdependent events.