Two neurons generated from a mouse radial glial cell, double labelled with a mouse-specific antibody (red) and the neuron-specific anti-β-tubulin-III (green). Image supplied by Paolo Malatesta, Max-Planck Institute of Neurobiology, Germany.

Traditional concepts of vertebrate neurogenesis, in which neurons and glia arise from separate, irreversibly committed lineages, are gradually being eroded. It has been shown that a subset of astrocytic cells in the adult brain can give rise to neurons, suggesting either that these cells are able to de-differentiate or that they are less committed to the glial lineage than was previously supposed. In a new paper in Development, Malatesta et al. show that radial glial cells also demonstrate a rarely recognized potential for neuronal differentiation.

The radial glia appear in the developing cerebral cortex around the time of onset of neurogenesis, which is embryonic day 11 (E11) in the mouse brain. They send out long processes that extend from the ventricular zone to the pial surface, forming a scaffold to guide neuronal migration. Their marker expression profile has placed them in the astrocytic lineage, and a role as glial progenitor cells has already been established.

Using fluorescence-activated cell sorting, Malatesta et al. isolated individual radial glia from the mouse cortex at various stages of embryonic development. Two different criteria were used to select the cells: the expression of green fluorescent protein (GFP) under the human promoter of the astrocytic marker GFAP and the presence of long radial processes. These processes could be labelled from the pial surface of the intact brain using a fluorescent retrograde tracer. It was confirmed that the sorted cells expressed markers characteristic of radial glia, including RC2, GLAST and BLBP. The differentiation potential of the isolated cells was analysed in co-culture with rat cortical cells to replicate their normal developmental environment. Of the cells isolated from the E14 cortex, half gave rise only to neuronal clones under these conditions and the rest generated mostly astroglia. By contrast, radial glia isolated from the cortex later during development (E18) gave rise mostly to astrocytes, suggesting that the differentiation potential of the radial glia becomes more restricted as development proceeds. Intriguingly, the radial glia demonstrating the highest level of neurogenic potential were isolated at a stage during which the brain is most active in neurogenesis, raising the possibility that these cells could be acting as neuronal precursors in vivo as well as in vitro.