Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia

Abstract

Neocortical basal radial glia (bRG) and cerebellar Bergmann glia (BG) are basal progenitors derived from ventricular apical radial glia (aRG) that selectively lose their apical processes. bRG and BG have been implicated in the expansion and folding of the cerebrum and cerebellum, respectively. Here, we analyzed the molecular characteristics and development of bRG and BG. Transcriptomic comparison revealed striking similarity of the molecular features of bRG and BG. We found that heightened ERK signaling activity in aRG is tightly linked to the temporal formation and the relative abundance of bRG in human and mouse cortices. Forced activation of an FGF-ERK-ETV axis that is crucial to BG induction specifically induced bRG with canonical human bRG features in mice. Therefore, our data point to a common mechanism of bRG and BG generation, bearing implications to the role for these basal progenitors in the evolution of cortical folding of the cerebrum and cerebellum.

DOI: http://dx.doi.org/10.7554/eLife.23253.001

eLife digest

The outer layer of the brain of a mammal, called the cortex, helps support mental abilities such as memory, attention and thought. In rodents, the cortex is smooth whereas in primates it is organized into folds. These folds increase the surface area of the brain and thus the number of neurons it can contain, which may in turn increase its processing power. Folding occurs as the brain develops in the womb. Specialized cells called basal or outer radial glia, which are more abundant in humans than in rodents, are believed to trigger the folding process.

Another area of the brain, called the cerebellum, is intricately folded in both rodents and humans. As the brain develops, cells within the cerebellum called Bergmann glia cause the tissue to fold. Bergmann glia and basal radial glia share a number of similarities, but it was not known whether the same molecular pathway might regulate both types of cell.

Now, Heng et al. show that Bergmann glia in the cerebellums of mice and basal radial glia in human cortex contain similar sets of active genes. Moreover, the molecular pathway that gives rise to Bergmann glia in mice is also active in the cortex of both mice and humans. However, it is much more active in humans, leading Heng et al. to speculate that high levels of activity in this pathway might give rise to basal radial glia. Consistent with this prediction, artificially activating the pathway at high levels in mouse cortex triggered the formation of basal radial glia in mice too. These results thus suggest that a common mechanism generates both types of glial cells involved in brain folding.

The work of Heng et al. lays the foundations for further studies into how these cells fold the brain and thus how they contribute to more complex mental abilities. Remaining questions to address are whether other species with Bergmann glia also have folded cerebellums, and whether incorrect development of basal radial glia in humans leads to disorders in which the cortex folds abnormally.

DOI: http://dx.doi.org/10.7554/eLife.23253.002