Programmed cell death in the developing human telencephalon

Programmed cell death (PCD) in the form of apoptosis is recognized as one o f the central events in the development of the central nervous system. To s tudy the time of onset, extent and distribution of PCD in the human telence phalon, embryos and fetuses from 4.5 to 27 gestational weeks (g.w.) were ex amined using the TUNEL (TdT-mediated dUTP-biotin nick-end labelling) in sit u method. At 4.5 g.w. sparse TUNEL(+) nuclei were observed in the ventricul ar zone of the neural tube. With the formation of the cortical plate at 7-8 g.w., TUNEL(+) nuclei were seen in all developmental layers of the cortica l anlage, as well as in the subcortical regions such as the ganglionic emin ence and the internal capsule. The proliferative zones (the ventricular zon e, the subventricular zone and the ganglionic eminence) contained the major ity of all apoptotic nuclei observed in each specimen. However, the apoptot ic index was highest in the subplate zone and in layer I. Double-labelling experiments suggested that neuronal precursors were the main population of cells undergoing PCD in the first trimester of gestation, whereas glial cel ls probably start dying around midgestation. The onset of labelling of micr oglial cells and apoptotic nuclei were synchronous, indicating the involvem ent of microglia in PCD. In conclusion, two distinct types of PCD were obse rved during human telencephalic development: embryonic apoptosis, which was synchronous with proliferation and migration of neuronal cells and probabl y not related to establishment of neuronal circuitry, and fetal apoptosis, which coincided with differentiation and synaptogenesis, and therefore may be related to the development of axonal-target connectivity.