Neuronal Restricted Precursors

Abstract

The extrinsic and intrinsic factors involved in regulating the developmental progression from totipotent embryonic stem cells to phenotypically restricted neural stem and progenitor cells have been subjects of intense research over the last decade. Two major reasons for this concentrated effort are the gradual acceptance that at least some regions of the brain generate neurons throughout life, and the growing appreciation that these cells could be used to therapeutically treat disorders and injuries of the central nervous system (CNS). Despite early studies by Altman and Das (1) demonstrating ongoing neurogenesis in the adult rodent hippocampus and olfactory bulb, it was widely believed until recently that in mammals the generation of neurons ceases in the late embryonic or early postnatal period. In addition to the persistent neurogenesis in the olfactory bulb and hippocampus, olfactory receptor neurons (ORNs), the first-order neurons in the peripheral olfactory system, were also found to regenerate throughout life in all vertebrates examined (2–4). Postnatal neurogenesis also occurs in the neonatal cerebellum (see ref. 1), although it is more limited in duration than that of the olfactory bulb, the hippocampus, and the ORNs. Populations of neural progenitor cells, which generate the neurons and/or glia in these regions with extended proliferation, have now been identified in the postnatal brain (5–11).