Editorial: To be glial or not—how glial are the precursors of neurons in development and adulthood?

In this special issue of Glia, our goal was to assemble the expertise of an emerging area of neurogenesis research that is focusing on the contribution of glial cells to the generation of neurons and their role as adult neural precursors. In contrast to the widespread neurogenesis throughout adulthood in most vertebrates (Zupanc and Clint, this issue), hardly any new neurons are formed in most CNS regions of mammals, with the consequence that degenerating neurons are usually not regenerated. In fact, it was long thought that neurogenesis could not exist at all in the mammalian brain, and certainly not in the brain of primates or humans (Gross, 2000) due to the concept that new neurons would only confuse the sophisticated neural networks of higher mammals. This was probably why the early evidence for neurogenesis in a few regions of the adult mammalian forebrain was long neglected by most of the scientific community. With new techniques, however, it became increasingly clear that neurogenesis also occurs in at least two regions of the mammalian forebrain: the subventricular zone (SVZ) of the basal ganglia, and the subgranular zone (SGZ) of the dentate gyrus. Moreover, from the very same regions, some precursors could be isolated and expanded in vitro that then exhibit the potential to generate all three main cell types of the CNS: astrocytes, neurons, and oligodendrocytes (Reynolds and Weiss, 1992; Richards et al., 1992). Thus, at least in vitro, these cells isolated from the adult mammalian forebrain exhibit the characteristics of stem cells including the potential of self-renewal. The apparent plasticity of these adult neural precursors after in vitro expansion, and their contribution to neurogenesis in vivo, substantiated the hope that these cells might be used at some point to reconstitute degenerating neurons within the context of various neurological diseases. To achieve the goal of neuronal repair, however, we need to understand how to influence the type of neuron generated by these adult neural precursors. An obvious first prerequisite for this aim was to identify these neural precursors in the adult mammalian forebrain, in order to isolate them, examine their gene expression, and study their cellular behavior. This proved to be not an easy task, however, as these cells are so rare, but eventually their self-renewal capacity could be exploited to identify them as astrocytes in both the SVZ and the SGZ (Doetsch et al., 1999; Seri et al., 2001). In contrast, the finding that ependymal cells can form neurospheres and act as slow dividing precursors generating precursors for neurons in vivo (Johansson et al., 1999) could not be reproduced by other groups (Chiasson et al., 1999; Laywell et al., 2000; Capela and Temple, 2002). Since then, the implication of glial cells in neurogenesis has gained considerable support in the adult, as well as the developing CNS, prompting us to combine reviews on the role of glial cells in neurogenesis in this special issue of Glia. We have brought together experts on neurogenesis from the radial glia during the development of the CNS (Campbell; Kriegstein and Götz and Morest and Silver, this issue); on the role of radial glia in cell migration (Morest and Silver; and Nadarajah; and Rakic, this issue); on the developmental transformation of radial glia into more differentiated glia, such as Müller cells and astrocytes (Fischer and Reh; Hall et al.; Marshall et al.; and Steindler and Laywell, this issue); and on the possibility that these more mature cells also may revert to their earlier more immature and possibly neurogenic status (Fischer and Reh; Steindler and Laywell; Zupanc and Clint; Messing and Brenner; Privat, this issue). We have deliberately asked the contributors for opinion papers rather than complete overviews, to allow the different views on these very recent data to emerge, with the aim that the readers develop their own views on such controversial issues. Obviously, these reviews are not only very timely, but they are also rather appropriate for the readership