Neuronal Cell Specification from CNS Stem Cells

Abstract

Little is known about the factors and pathways leading to the production of neurons of the mammalian central nervous system (CNS). Although many in vitro and in vivo studies have described the presence of both unipotent and multipotent CNS progenitor cells and their regulation by extrinsic signaling molecules (reviewed in McKay, 1989), the pathways from primitive precursor to differentiated neuron have not been identified. This is contrasted by cells of the lympho-hematopoietic system, whereby a number of pathways leading from the primitive hematopoietic precursors to fully differentiated blood and immune cells have been described (Metcalf, 1989). Our lack of understanding regarding CNS cell production is due, partially, to a paucity of descriptions of primitive CNS precursors. Recently, we have isolated a cell from the embryonic (Reynolds et al., 1992) and adult (Reynolds and Weiss, 1992) mammalian CNS that fulfills the criteria representative of a stem cell. In this chapter, we review a series of studies which suggest that the pathway from CNS stem cell to differentiated neurons may involve the sequential actions of growth factors that act to influence undifferentiated neural precursors towards the neuronal lineage.