Neurons derived from radial glial cells establish radial units in neocortex

The neocortex of the adult brain consists of neurons and glia that are generated by precursor cells of the embryonic ventricular zone. In general, glia are generated after neurons during development(1), but radial glia are an exception to this rule. Radial glia are generated before neurogenesis and guide neuronal migration(2). Radial glia are mitotically active throughout neurogenesis(3), and disappear or become astrocytes when neuronal migration is complete(4,5). Although the lineage relationships of cortical neurons and glia have been explored(6,7), the clonal relationship of radial glia to other cortical cells remains unknown. It has been suggested that radial glia may be neuronal precursors(5,8-10), but this has not been demonstrated in vivo. We have used a retroviral vector encoding enhanced green fluorescent protein to label precursor cells in vivo and have examined clones 1-3 days later using morphological, immunohistochemical and electrophysiological techniques. Here we show that clones consist of mitotic radial glia and postmitotic neurons, and that neurons migrate along clonally related radial glia. Time-lapse images show that proliferative radial glia generate neurons. Our results support the concept that a lineage relationship between neurons and proliferative radial glia may underlie the radial organization of neocortex.