Neural progenitor cells and developmental disorders

Neural stem/multipotent progenitor cells are present within periventricular generative zones along the entire neuraxis throughout neural development and during adult life. These cells give rise to all of the major cellular elements of the brain, including neurons, oligodendroglia, and astrocytes. Recent studies suggest that cells with a similarly broad lineage potential are also present in postmigratory domains of the postnatal and the adult cerebral cortex. Neural stem cells are defined by a number of properties, including their ability to undergo constitutive proliferation, to maintain themselves (self-renew), to generate large numbers of progeny through transient amplification of intermediate progenitor pools, and to generate new cells in response to injury or disease. These primordial neural cells undergo progressive lineage restriction and commitment to specific neuronal and glial phenotypes in response to cascades of cytokines and the induction of positive and negative transcriptional regulators. These cytokines regulate a range of interrelated cellular processes, including activation, proliferation, viability, lineage commitment, and progressive stages of neuronal and glial lineage maturation. The detailed definition of developmental pathways responsible for neurogenesis and gliogenesis in the mammalian brain will further our understanding of the molecular and cellular basis of mental retardation and other pervasive neurologic disorders of childhood. Further, these cumulative studies suggest that a broad array of neural regenerative strategies, including gene and progenitor cell replacement and activation of endogenous cellular populations, may allow structural and functional reconstitution of neural circuits damaged as a consequence of a spectrum of neurodevelopmental disorders.