Radial glial cells as neuronal precursors: the next generation?

Abstract

One of the major challenges in precursor cell biology of the central nervous system (CNS) has been to unambiguously identify different precursor cells so that we may better study them. Precursors have been largely characterized by the cell types they produce, compelling us to study them retrospectively without knowledge of which particular cell gave rise to specific progeny. Radial glial cells, easily identifiable cell types in the embryonic germinal zone, have been suggested recently to comprise a significant proportion of the neuronal precursor cell population of the developing brain (Malatesta et al., 2000; Miyata et al., 2001; Noctor et al., 2001, 2002). Radial glia can be identified by their characteristic bipolar morphology in which the cell soma resides in the ventricular zone (VZ) or subventricular zone (SVZ), bearing a long basal process that extends outwards toward the pial surface and a second, short apical process that contacts the ventricular wall. The existence of such cells has long been recognized and they have borne many names over the course of the field’s history (Bentivoglio and Mazzarello, 1999). Pasko Rakic recognized that these cells express the astrocytic marker glial fibrillary acidic protein (GFAP) in the developing primate CNS and termed them “radial glia” (Rakic, 1972; Levitt and Rakic, 1980). In the mouse these cells do not begin to express GFAP until late in embryonic development, but can be identified with several other specific markers, including RC2 (Misson et al., 1988), brain lipidbinding protein (BLBP; Feng et al., 1994), vimentin (Dahl et al., 1981), nestin (Hockfield and McKay, 1985) and GLAST (Shibata et al., 1997). Rakic went on to show that radial glial cells act as a scaffold to support the migration of newly generated neurons from the embryonic germinal zone into the developing layers of the cortex, and until recently this was considered to be the major role for radial glial cells, before their postnatal transdifferentiation into astrocytes. The new role for radial glial cells as neuronal precursor cells in the embryo may dramatically change our understanding of CNS development, yet, at the same time, it raises several important and possibly controversial issues. In this mini-review, we critically examine our present understanding of radial glial cell regulation, specifically regarding the processes of induction, maintenance, and transdifferentiation. We also discuss our knowledge of cell lineage in the developing forebrain as it pertains to a putative role for radial glia as the major precursor population in vivo.