Neurons derived from radial glial cells establish radial units in neocortex

Abstract

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 development1, but radial glia are an exception to this rule. Radial glia are generated before neurogenesis and guide neuronal migration2. Radial glia are mitotically active throughout neurogenesis3, and disappear or become astrocytes when neuronal migration is complete4,5. Although the lineage relationships of cortical neurons and glia have been explored6,7, the clonal relationship of radial glia to other cortical cells remains unknown. It has been suggested that radial glia may be neuronal precursors5,8,9,10, 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.

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Figure 1: Radial clonal units 24–72 h after retroviral infection.
Figure 2: Radial clones contain mitotic radial glial cells.
Figure 3: Radial clones contain radial glia and immature neurons.
Figure 4: Time-lapse videomicroscopy of radial glial cell division.

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Acknowledgements

We thank D. Owens for comments on the manuscript; W. Wong, B. Clinton, A. Kakita, A. Milosevic and E. Benardete for technical assistance; and J. Goldman for providing the 293gp NIT–GFP retrovirus packaging cell line. Supported by grants from the NIH and grants from the March of Dimes Birth Defects Foundation, the Lieber Center and the Robert Lee and Clara Guthrie Patterson Trust.

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Correspondence to Arnold R. Kriegstein.

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Noctor, S., Flint, A., Weissman, T. et al. Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–720 (2001). https://doi.org/10.1038/35055553

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