Neuronal cell lineage in the vertebrate central nervous system

Fundamental, yet unresolved, issues in developmental neurobiology concern the relative influence of genetic vs. epigenetic factors in determining cell phenotype and establishing positional relationships among clonally related cells in the developing and mature vertebrate central nervous system (CNS). Advances in our understanding of how cells acquire their identity awaited a means to introduce lineage tracers into dividing cells of the developing CNS where the progenitor cells, which are situated in a neuroepithelial layer adjacent to the ventricles, generally are small and inaccessible. The technique of retroviral-mediated gene transfer, whereby a heritable, easily detectable marker such as the gene for lacZ is integrated into the DNA of individual progenitor cells, has been used to analyze the lineage relationships of cells in the CNS and to derive the types of progenitor cells in the proliferative zones at different developmental stages. Collectively, these studies indicate that the CNS uses more than one strategy to achieve cell diversity. The analysis of the phenotypic composition of the cells within a clone indicates that there are predominantly separate progenitor cells for each of the main cell types comprising the cerebral cortex by the onset of cortical neurogenesis, although in other systems mostly multipotential progenitor cells persist throughout neurogenesis. Here I will compare and contrast the inferred role of cell lineage in the developing cerebral cortex and olfactory bulb, where postmitotic neurons migrate relatively long distances from their site of generation to their final destination, with that in other regions of the CNS in which the displacement of postmitotic neurons from their birthplace is significantly less.