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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References
Boulder Committee. Embryonic vertebrate central nervous system: revised terminology. Anat. Rec. 166, 257–261 (1970).
Rakic, P. Mode of cell migration to the superficial layers of fetal monkey neocortex. J. Comp. Neurol. 145, 61–83 (1972).
Misson, J. P., Edwards, M. A., Yamamoto, M. & Caviness, V. S. Jr Mitotic cycling of radial glial cells of the fetal murine cerebral wall: a combined autoradiographic and immunohistochemical study. Brain Res. 466, 183–190 (1988).
Misson, J. P., Takahashi, T. & Caviness, V. S. Jr Ontogeny of radial and other astroglial cells in murine cerebral cortex. Glia 4, 138–148 (1991).
Chanas-Sacre, G., Rogister, B., Moonen, G. & Leprince, P. Radial glia phenotype: origin, regulation, and transdifferentiation. J. Neurosci. Res. 61, 357–363 (2000).
Luskin, M. B., Pearlman, A. L. & Sanes, J. R. Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a recombinant retrovirus. Neuron 1, 635–647 (1988).
Reid, C. B., Liang, I. & Walsh, C. Systematic widespread clonal organization in cerebral cortex. Neuron 15, 299–310 (1995).
McKay, R. D. The origins of cellular diversity in the mammalian central nervous system. Cell 58, 815–821 (1989).
Alvarez-Buylla, A., Theelen, M. & Nottebohm, F. Proliferation “hot spots” in adult avian ventricular zone reveal radial cell division. Neuron 5, 101–109 (1990).
Malatesta, P., Hartfuss, E. & Gotz, M. Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127, 5253–5263 (2000).
Mountcastle, V. B. The columnar organization of the neocortex. Brain 120, 701–722 (1997).
Rakic, P. Specification of cerebral cortical areas. Science 241, 170–176 (1988).
Pixley, S. K. & de Vellis, J. Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Brain Res. 317, 201–209 (1984).
Hockfield, S. & McKay, R. D. Identification of major cell classes in the developing mammalian nervous system. J. Neurosci. 5, 3310–3328 (1985).
LoTurco, J. J. & Kriegstein, A. R. Clusters of coupled neuroblasts in embryonic neocortex. Science 252, 563–566 (1991).
Bittman, K., Owens, D. F., Kriegstein, A. R. & LoTurco, J. J. Cell coupling and uncoupling in the ventricular zone of developing neocortex. J. Neurosci. 17, 7037–7044 (1997).
Anton, E. S., Kreidberg, J. A. & Rakic, P. Distinct functions of α3 and αv integrin receptors in neuronal migration and laminar organization of the cerebral cortex. Neuron 22, 277–289 (1999).
Austin, C. P. & Cepko, C. L. Cellular migration patterns in the developing mouse cerebral cortex. Development 110, 713–732 (1990).
Takahashi, T., Nowakowski, R. S. & Caviness, V. Jr Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse. J. Neurosci. 13, 820–833 (1993).
Price, J. & Thurlow, L. Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer. Development 104, 473–482 (1988).
Luskin, M. B., Parnavelas, J. G. & Barfield, J. A. Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells. J. Neurosci. 13, 1730–1750 (1993).
Cai, L., Hayes, N. L. & Nowakowski, R. S. Synchrony of clonal cell proliferation and contiguity of clonally related cells: production of mosaicism in the ventricular zone of developing mouse neocortex. J. Neurosci. 17, 2088–2100 (1997).
Gray, G. E. & Sanes, J. R. Lineage of radial glia in the chicken optic tectum. Development 114, 271–283 (1992).
Lewis, J. Notch signalling and the control of cell fate choices in vertebrates. Semin. Cell. Dev. Biol. 9, 583–589 (1998).
Austin, C. P., Feldman, D. E., Ida, J. A. Jr & Cepko, C. L. Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch. Development 121, 3637–3650 (1995).
Gaiano, N., Nye, J. S. & Fishell, G. Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26, 395–404 (2000).
Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A. & Fuchs, E. Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J. Neurosci. 17, 2492–2498 (1997).
Anderson, S. A., Eisenstat, D. D., Shi, L. & Rubenstein, J. Interneuron migration from basal forebrain to neocortex: dependence on dlx genes. Science 278, 474–476 (1997).
Gressens, P. & Evrard, P. The glial fascicle: an ontogenic and phylogenic unit guiding, supplying and distributing mammalian cortical neurons. Brain Res. Dev. Brain Res. 76, 272–277 (1993).
Blanton, M. G., LoTurco, J. J. & Kriegstein, A. R. Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex. J. Neurosci. Methods 30, 203–210 (1989).
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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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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DOI: https://doi.org/10.1038/35055553
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