Progenitor cell proliferation outside the ventricular and subventricular zones during human brain development

The ventricular zone (VZ) and subventricular zone (SVZ) of the fetal brain are generally believed to give rise to all the neurons and glia that will populate the cerebral hemispheres. In rodents a mitotically active cell (progenitor cell) has been identified outside the VZ and SVZ, in the intermediate zone (IZ) of the cerebral hemisphere. The cell types that arise from these progenitor cells remain uncertain. We have set out to determine if a similar population of mitotically active cells is present in the IZ during human brain development, and to try and define the cell type that arise from this progenitor cell. Using a monoclonal antibody that recognizes proliferating cell nuclear antigen (PCNA), a replication-specific protein, the cerebral hemispheres from 9 human fetal and infant brains between ages of 15 and 38 weeks gestation were studied. PCNA-immunopositive cells were found in the internal capsule and cerebral white matter with approximately equal frequency and rarely in the cerebral cortex between 15 and 20 weeks gestation. In the internal capsule, the number of positive cells decreased by the end of the second trimester; however, a relatively constant number of PCNA-positive cells remained in the cerebral white matter. By the last trimester relatively little staining was found in any of the regions studied. Anti-GFAP immunostaining indicated that at least some of these progenitors were in the glial lineage. These data provide direct evidence that, in addition to ventricular zone proliferation, a population of progenitor cells continue to proliferate within nascent white matter tracts during development.