Dividing Precursor Cells of the Embryonic Cortical Ventricular Zone Have Morphological and Molecular Characteristics of Radial Glia

Abstract

The embryonic ventricular zone (VZ) of the cerebral cortex contains migrating neurons, radial glial cells, and a large population of cycling progenitor cells that generate newborn neurons. The latter two cell classes have been assumed for some time to be distinct in both function and anatomy, but the cellular anatomy of the progenitor cell type has remained poorly defined. Several recent reports have raised doubts about the distinction between radial glial and precursor cells by demonstrating that radial glial cells are themselves neuronal progenitor cells (Malatesta et al., 2000; Hartfuss et al., 2001; Miyata et al., 2001; Noctor et al., 2001). This discovery raises the possibility that radial glia and the population of VZ progenitor cells may be one anatomical and functional cell class. Such a hypothesis predicts that throughout neurogenesis almost all mitotically active VZ cells and a substantial percentage of VZ cells overall are radial glia. We have therefore used various anatomical, immunohistochemical, and electrophysiological techniques to test these predictions. Our data demonstrate that the majority of VZ cells, and nearly all mitotically active VZ cells during neurogenesis, both have radial glial morphology and express radial glial markers. In addition, intracellular dye filling of electrophysiologically characterized progenitor cells in the VZ demonstrates that these cells have the morphology of radial glia. Because the vast majority cycling cells in the cortical VZ have characteristics of radial glia, the radial glial precursor cell may be responsible for both the production of newborn neurons and the guidance of daughter neurons to their destinations in the developing cortex.

Mechanism of stem cells in the central nervous system

“…The traditional view of radial glia cells is that of nonneuronal cells of the astroglial lineage found in the developing CNS and that neuroepithelial cells lining the ventricles, the germinal zone, give rise to distinct populations of neurons and glia, including the radial glia. However, compelling evidence that radial glial cells contribute to embryonic neurogenesis have been reported by several groups (Malatesta et al, 2000;Hartfuss et al, 2001;Miyata et al, 2001;Noctor et al, 2001Noctor et al, , 2002. Recently, it was demonstrated that Pax6 mutants have reduced neurogenesis.…”

The determination of projection neuron identity in the developing cerebral cortex

“…Direct evidence that the SVZ is a neurogenic zone has been derived from a recent series of elegant imaging experiments [19,20] in conjunction with related work from other labs [21][22][23]. Noctor and colleagues used time-lapse confocal time-lapse microscopy to track the behavior of individual GFP-labeled mitotic progenitors in the VZ and SVZ, and then to follow the behavior and fates of their daughter cells [19,24,25].…”

Neuronal stem cells in the central nervous system and in human diseases

“…RG cells have been traditionally characterized by their characteristic bipolar morphology and by their contact with both ventricular and pial surfaces. Whole-cell patch-clamp recordings with single-cell dye labeling have revealed the morphology and measured the membrane properties of randomly chosen cells in contact with the ventricular surface, suggesting that cells with the characteristic morphological features of RG cells have the physiological features of precursor cells (LoTurco et al, 1991;Noctor et al, 2002). Similarly, the application of DiI or fluorescent microbeads to the pial surface of developing neocortex labels mitotically active VZ cells with distinct RG morphology (Malatesta et al, 2000;Miyata et al, 2001), and has demonstrated that these cells constitute more than 90% of mitotically active cells in the VZ (Noctor et al, 2002(Noctor et al, , 2004.…”

“…During mitosis, several studies have illustrated that RG cells remain in place without retraction from the pial surface throughout the whole cell cycle (Miyata et al, 2001;Noctor et al, 2001Noctor et al, , 2002Tamamaki et al, 2001;Weissman et al, 2004). Within the radial fiber of RG cells, the cytoplasm climbs toward the cell body with varicosities showing at intervals along the attenuated fiber (Miyata et al, 2001;Noctor et al, 2001Noctor et al, , 2002Tamamaki et al, 2001;Weissman et al, 2004).…”

“…Within the radial fiber of RG cells, the cytoplasm climbs toward the cell body with varicosities showing at intervals along the attenuated fiber (Miyata et al, 2001;Noctor et al, 2001Noctor et al, , 2002Tamamaki et al, 2001;Weissman et al, 2004). In addition to generating neurons, RG cells supply the fibers for neuronal migration (Rakic, 1978).…”