Stem cells in neurodevelopment and plasticity.

The processes of stem cell proliferation and differentiation during embryogenesis are governed by transcription factors that regulate the regional differentiation of the central nervous system (CNS). Do neural "stem" cells persisting in the postnatal CNS disobey this sequence of events? The division of neural progenitor cells is promoted by basic Fibroblast Growth Factor Fgf2 or Epidermal Growth Factor Egf. However, while the intraventricular administration of FgF2 during embryogenesis increases the generation of cortical pyramidal neurons, the same treatment in the adult CNS produces interneurons of the olfactory bulb. The competence of neural progenitor cells to respond to Fgf is dictated by nuclear transcription factors that constrain neuronal fates through time. Developmentally regulated transcriptional programs are regulated by cell interactions, as dividing cells check their molecular signature against that of their environment. Thus, cell surface interactions account for competitive phenomena among pools of cells, including the inhibitory effect of neurons on the division of their progenitors, and may also explain the "permissive" effects of non-CNS environments. The challenge remains to understand the genetic programs that control the fate of progenitor cells within the postnatal CNS and their regulation by stress, apoptosis and environmental perturbations. These programs are likely to be similar to gene cascades that control proliferation, differentiation and migration of progenitor cells at earlier stages of development.