NEURAL PROGENITOR CELLS AND DEVELOPMENTAL DISORDERS

Neural stem/multipotent progenitor cells are present within periventri cular generative zones along the entire neuraxis throughout neural dev elopment and during adult life. These cells give rise to all of the ma jor cellular elements of the brain, including neurons, oligodendroglia , and astrocytes. Recent studies suggest that cells with a similarly b road lineage potential are also present in postmigratory domains of th e postnatal and the adult cerebral cortex. Neural stem cells are defin ed by a number of properties, including their ability to undergo const itutive proliferation, to maintain themselves (self-renew), to generat e large numbers of progeny through transient amplification of intermed iate 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, proliferati on, 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 mammalia n brain will further our understanding of the molecular and cellular b asis of mental retardation and other pervasive neurologic disorders of childhood. Further, these cumulative studies suggest that a broad arr ay of neural regenerative strategies, including gene and progenitor ce ll replacement and activation of endogenous cellular populations, may allow structural and functional reconstitution of neural circuits dama ged as a consequence of a spectrum of neurodevelopmental disorders. (C ) 1998 Wiley-Liss, Inc.