Cells in the astroglial lineage are neural stem cells

Abstract

A common assumption of classical neuroscience was that neurons and glial cells were derived from separate pools of progenitor cells and that, once development was completed, no new neurons were produced. The subsequent disproving of the "no new neuron" dogma suggested that ongoing adult neurogenesis was supported by a population of multipotent neural stem cells. Two germinal regions within the adult mammalian brain were shown to contain neural progenitor cells: the subventricular zone (SVZ) along the walls of the lateral ventricles, and the subgranular zone (SGZ) within the dentate gyrus of the hippocampus. Surprisingly, when the primary progenitors (stem cells) of the new neurons in these regions were identified, they exhibited structural and biological markers of astrocytes. The architecture of these germinal regions and the pattern of division of neural stem cells have raised fundamental questions about the mechanism of adult neurogenesis. This review describes studies on the origin of adult neural stem cells, the features distinguishing them from astrocytes in non-germinal regions, and the control mechanisms of the proliferation and differentiation of these cells. Astrocytic adult neural stem cells are part of a developmental lineage extending from the neuroepithelium to radial glia to germinal astrocytes. Adult neural stem cells appear to be strongly influenced by their local microenvironment, while also contributing significantly to the architecture of these germinal zones. However, environment alone does not seem to be sufficient to induce non-germinal astrocytes to behave as neural stem cells. Although emerging evidence suggests that significant heterogeneity exists within populations of germinal zone astrocytes, the way that these differences are encoded remains unclear. The further characterization of these cells should eventually provide a body of knowledge central to the understanding of brain development and disease.

Differentiation capacity of native pituitary folliculostellate cells and brain astrocytes

“…they act as supportive cells and produce S100B protein specifically in the brain and in the pituitary gland (Koehler et al 2006, Straub & Nelson 2007. Some astrocytes may reportedly act as neural stem cells in the brain and form neurospheres, which can generate neurons and glial cells (Laywell et al 2000, Alvarez-Buylla & Lim 2004, Ihrie & Alvarez-Buylla 2008. Although the reported differentiation potential of astrocytes is restricted to the neurons or glial cells, this study shows that astrocytes can also differentiate to express a number of key characteristics of muscle.…”

Discovery of a functional protein complex of netrin-4, laminin γ1 chain, and integrin α6β1 in mouse neural stem cells

“…Astrocyte production of laminin and other extracellular matrix components such as tenascin-C and chondroitin sulfate has been demonstrated under both normal and pathological conditions (29,37). To add further levels of complexity and diversity, there appear to be multiple subsets of GFAP-expressing astrocytes in the olfactory system, distinguished by whether or not they express surface markers such as vimentin and nestin (38,39). The subset of astrocytes that we have shown to contain netrin-4 may be involved in multiplication and migration of those neuron precursors, reviewed by Ihrie and Alvarez-Buylla (39), destined for the glomerular layer of the OB and arising not in the SVZ of the lateral ventricle, but in the less widely recognized prebulbar sector of the RMS.…”

Micromanipulation of Gene Expression in the Adult Zebrafish Brain Using Cerebroventricular Microinjection of Morpholino Oligonucleotides

“…Therefore, investigating the molecular basis of the regenerative aptitude of zebrafish brain is an interesting realm of research that might explain the fundamental difference how fish and mammalian brains react after an injury, and also endow avenues for regenerative medical therapies in humans. In order to understand the molecular infrastructure of vertebrate brain plasticity and regeneration, glial cells serve as an important research area as they are the neurogenic progenitors 3,8,20 . Thus, using CVMI technique to alter gene function in the radial glial cells of the zebrafish brain is instrumental in elucidating how fish brain can couple progenitor activity to efficient adult neurogenesis and regenerative response.…”

“…For instance, adult mammalian brains contain stem cell regions largely restricted to the forebrain 7,8 , while the teleost zebrafish contains sixteen different stem cell domains and associated neurogenic zones in its entire brain 4,5,9,10 . This variation between mammals and zebrafish might reflect a disparity in the mechanisms of stem cell maintenance and the neurogenic capacity of the progenitor cells.…”