Programmed cell death is a universal feature of embryonic and postnatal neuroproliferative regions throughout the central nervous system

Abstract

During central nervous system (CNS) development, programmed cell death (PCD) has been viewed traditionally as a fate reserved for differentiating neurons that are in the process of making synaptic connections. Recent studies in the embryonic cerebral cortex (Blaschke et al. [1996] Development 122:1165-1174), however, have shown that many neuroblasts in the proliferative ventricular zone undergo PCD as well and that this likely represents a novel form distinct from that found in regions of postmitotic neurons. To determine the commonality of this form of PCD throughout the CNS, the prevalence of dying cells identified by in situ end labeling plus (ISEL +; Blaschke et al. [1996]) was determined within populations of proliferating neuroblasts that were identified by rapid bromodeoxyuridine incorporation. Based on this approach, dying cells were observed to be a common feature of all proliferative neuroblast populations examined. In addition, when ISEL+ was combined with in situ hybridization for postmitotic neural gene-1 (png- 1; Weiner and Chun [1997] J. Comp. Neurol. 381:130-142), which identifies newly postmitotic neurons, a positive correlation was found between the start of differentiation and the onset of PCD. These data indicate that PCD in neuroblast proliferative zones is a universal feature of nervous system development. Moreover, cell death represents a prominent cell fate that may be linked to mechanisms of differentiation.