The (not necessarily) convoluted role of basal radial glia in cortical neurogenesis

Abstract

Recent advances in cell labeling and imaging techniques have dramatically expanded our knowledge of the neural precursor cells responsible for corticogenesis. In particular, radial glial cells are now known to generate several classes of restricted progenitors and neurons. While radial glial cells in the ventricular zone have received the most attention, it has become increasingly clear that a distinct subclass of radial glial cells situated in the subventricular zone (SVZ) and intermediate zone also play an important role in corticogenesis. These delaminated radial glial cells, which lack an apical process attached to the ventricular surface but maintain a basal process, were discovered over 3 decades ago. Recently, they have been further characterized as cortical progenitors and renamed outer, intermediate, or basal radial glia (bRG). Some of these studies indicated that bRG abundance in the outer SVZ (oSVZ) is correlated with enhanced gyrencephaly, particularly in primates and especially human, and therefore suggested that bRG may be responsible for the emergence and evolution of cerebral convolutions. In this issue of Cerebral Cortex, 2 papers provide new information about bRG in common marmosets, a near-lissencephalic primate, and in agouti, a near-gyrencephalic rodent (Garcia-Moreno et al. 2011; Kelava et al. 2011). They demonstrate that bRG are abundant and proliferate in inner as well as oSVZ, in both species. Together, these findings indicate that bRG and the oSVZ might not be correlated with gyrification or phylogeny. Rather, differential regulation of bRG and other progenitor types may enhance the adaptability and diversity of cortical morphogenesis.

Figure 1.

Neurogenic progenitors in developing neocortex. (A) Schematic illustration of cortical progenitor lineages, compartments, and characteristic transcription factor expression. aRG generate cortical projection neurons (PNs) directly and indirectly via bRG, apical intermediate progenitors (aIPs), and basal intermediate progenitors (bIPs). In addition, basal “nonradial” glia (bNG) have been described in human cortex (Hansen et al. 2010) and SNPs in rodent cortex. Colors indicate the capacity for proliferation and self-renewal: black, high; light blue, low; dark blue, postmitotic; gray, unknown. (B) Examples of progenitors identified by transcription factor expression in embryonic day (E) 14.5 mouse neocortex. Radial glia are identified by high Pax6 (green) expression and IPs by Tbr2 (red) expression. At this stage, most radial glia are aRG located in the VZ and most IPs are bIP in the SVZ and aIP in the VZ. The boxed area, enlarged at right, contains 3 progenitor cells interpreted as a bRG (green arrowhead), a newly generated bIP (yellow arrowhead), and a mature bIP (red arrowhead).

Figure 2.

Distribution of aRG and bRG in developing cortex of 5 species. Mouse cortex (A) contains a low number of bRG and has a lissencephalic cortex with very low gyrification index (GI) of 1.03. Marmoset cortex (B) has abundant bRG in iSVZ and oSVZ, despite a low GI of 1.2. Agouti (C) contains relatively abundant bRG in oSVZ and iSVZ. Ferret (D) and human (E) cortex contain abundant bRG, most of which are located in the oSVZ. Zones and progenitor types indicated as in Figure 1.