Subependymal zone

Abstract: The properties and fate of the cells of the subependymal layer of the anterior lateral ventricle and its rostral extension into the olfactory bulb were exam­ ined. In one experiment, histological analysis was made of this structure in a large group of rats, ranging in age from newborn to adults. It was established that the ventricular subependymal layer and its rostral extension are present as proliferative and migratory matrices throughout the period studied, with relatively little reduction in size from birth to adulthood. In another, autoradiographic study, the proliferation and migration of cells of this system, and their destination and mode of differentiation, were studied in rats that were injected with thymidine-H3 at 30 days of age and killed at intervals ranging from 1 hour to 180 days. There was a declining gradient in cell proliferation in a caudorostral direction from a high level near the lateral ventricle to the absence of cell proliferation in the olfactory bulb. The labeled cells that were present in high proportion near the lateral ventricle in the rats killed 1-24 hours after injection had further multiplied and moved to the middle portion of the "rostral migratory stream" by the third day, and were located in the subependymal layer of the olfactory bulb by the sixth day after injection. By the twentieth day the labeled ceHs disappeared from the subependymal layer of the olfac­ tory bulb and were distributed throughout the internal granular layer. The differ­ entiated cells were tentatively identified as granular nerve cells and neuroglia cells. These results established that the major target structure of cell production in the subependymal layer of the lateral ventricle in young-adult rats is the olfactory bulb, with only moderate contribution made to the anterior neocortex and basal ganglia. It was postulated that the function of cell migration to the olfactory bulb is the renewal of its cell population. Several investigators (Allen, '12; Bryans, graphic investigation, Smart examined '59; Globus and Kuhlenbeck, '44; Opalski, the morphology of this subependymallayer '34 Rydberg, '32) reported the presence in in infant and adult mice. He established adult animals and man of a mitotically ac­ that the proliferative subependymal layer tive "subependymal layer" (Kershman, '38) extended in adult mice from the anterior around the ependymal wall of the anterior wall of the lateral ventricle rostrally into lateral ventricle. Because techniques were the olfactory bulb. Smart's results indi­ not available for tagging these cells, these cated that these cells give rise, in infant earlier investigators could only speculate mice, to glia and neurons, but he failed to about their fate. The technique of thymi­ obtain evidence of migration in adult mice dine-H" autoradiography, which can be used (excepting a few cells that seemed to for tagging newly-forming cells in order to "leak" into the corpus callosum). He postu­ trace their destiny, was first addressed to lated, in agreement with the hypothesis of this problem by Messier et al. ('58) and previous investigators, that the mitotic ac­ more particularly by Smart ('61). In a tivity of this layer in adults is an abortive combined histological and autoradio- phenomenon and the newly-forming cells

Abstract: Much excitement has been generated by the identification of adult brain regions harboring neural stem cells and their continual generation of new neurons throughout life. This is an important departure from traditional views of the germinal potential of the postnatal brain. However, a more profound

Abstract: Establishing the cellular identity in vivo of adult multipotent neural progenitors is fundamental to understanding their biology. We used two transgenic strategies to determine the relative contribution of glial fibrillary acidic protein (GFAP)-expressing progenitors to constitutive neurogenesis in the adult forebrain. Transgenically targeted ablation of dividing GFAP-expressing cells in the adult mouse subependymal and subgranular zones stopped the generation of immunohistochemically identified neuroblasts and new neurons in the olfactory bulb and the hippocampal dentate gyrus. Transgenically targeted cell fate mapping showed that essentially all neuroblasts and neurons newly generated in the adult mouse forebrain in vivo, and in adult multipotent neurospheres in vitro, derived from progenitors that expressed GFAP. Constitutively dividing GFAP-expressing progenitors showed predominantly bipolar or unipolar morphologies with significantly fewer processes than non-neurogenic multipolar astrocytes. These findings identify morphologically distinctive GFAP-expressing progenitor cells as the predominant sources of constitutive adult neurogenesis, and provide new methods for manipulating and investigating these cells.