A double-labeling technique, combining retroviral tagging of individual cell lines (one clone per brain hemisphere) with the simultaneous [3H]thymidine-labeling of dividing cells in S phase, was used to study proliferation characteristics of individual precursor cell lines in the germinal zone of the developing rat forebrain. The cortical germinal zone was found to be segregated into three spatially distinct horizontal populations of precursor cell lineages, which differed in cell cycle kinetics, amount of cell death, and synchronous versus asynchronous mode of proliferation. The striatal germinal zone demonstrated a similar heterogeneity in the cell cycle characteristics of proliferating clones, but did not show nearly as distinct a spatial segregation of these different populations. The results demonstrate the clonal heterogeneity among precursor populations in the telencephalon and the differential spatial organization of the cortical and the striatal germinal zones. This germinal zone heterogeneity may predict some of the differences found among cellular phenotypes in the adult forebrain.
DNA Methylation and Intra-Clonal Heterogeneity: The Chronic Myeloid Leukemia Model
