Movatterモバイル変換

[0]ホーム
URL:

Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Nature
  • Letter
  • Published:

Neurons derived from radial glial cells establish radial units in neocortex

Naturevolume 409, pages714–720 (2001)Cite this article

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 demonstratedin vivo. We have used a retroviral vector encoding enhanced green fluorescent protein to label precursor cellsin 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.

This is a preview of subscription content,access via your institution

Access options

Access through your institution

Subscription info for Japanese customers

We have a dedicated website for our Japanese customers. Please go tonatureasia.com to subscribe to this journal.

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

￥ 4,980

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Boulder Committee. Embryonic vertebrate central nervous system: revised terminology.Anat. Rec.166, 257–261 (1970).

    Article  Google Scholar 

  2. Rakic, P. Mode of cell migration to the superficial layers of fetal monkey neocortex.J. Comp. Neurol.145, 61–83 (1972).

    Article CAS PubMed  Google Scholar 

  3. 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).

    Article CAS PubMed  Google Scholar 

  4. Misson, J. P., Takahashi, T. & Caviness, V. S. Jr Ontogeny of radial and other astroglial cells in murine cerebral cortex.Glia4, 138–148 (1991).

    Article  Google Scholar 

  5. Chanas-Sacre, G., Rogister, B., Moonen, G. & Leprince, P. Radial glia phenotype: origin, regulation, and transdifferentiation.J. Neurosci. Res.61, 357–363 (2000).

    Article CAS PubMed  Google Scholar 

  6. 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.Neuron1, 635–647 (1988).

    Article CAS PubMed  Google Scholar 

  7. Reid, C. B., Liang, I. & Walsh, C. Systematic widespread clonal organization in cerebral cortex.Neuron15, 299–310 (1995).

    Article CAS PubMed  Google Scholar 

  8. McKay, R. D. The origins of cellular diversity in the mammalian central nervous system.Cell58, 815–821 (1989).

    Article CAS PubMed  Google Scholar 

  9. Alvarez-Buylla, A., Theelen, M. & Nottebohm, F. Proliferation “hot spots” in adult avian ventricular zone reveal radial cell division.Neuron5, 101–109 (1990).

    Article CAS PubMed  Google Scholar 

  10. Malatesta, P., Hartfuss, E. & Gotz, M. Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage.Development127, 5253–5263 (2000).

    CAS PubMed  Google Scholar 

  11. Mountcastle, V. B. The columnar organization of the neocortex.Brain120, 701–722 (1997).

    Article PubMed  Google Scholar 

  12. Rakic, P. Specification of cerebral cortical areas.Science241, 170–176 (1988).

    Article ADS CAS PubMed  Google Scholar 

  13. 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).

    Article CAS PubMed  Google Scholar 

  14. Hockfield, S. & McKay, R. D. Identification of major cell classes in the developing mammalian nervous system.J. Neurosci.5, 3310–3328 (1985).

    Article CAS PubMed PubMed Central  Google Scholar 

  15. LoTurco, J. J. & Kriegstein, A. R. Clusters of coupled neuroblasts in embryonic neocortex.Science252, 563–566 (1991).

    Article ADS CAS  Google Scholar 

  16. 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).

    Article CAS PubMed PubMed Central  Google Scholar 

  17. 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.Neuron22, 277–289 (1999).

    Article CAS PubMed  Google Scholar 

  18. Austin, C. P. & Cepko, C. L. Cellular migration patterns in the developing mouse cerebral cortex.Development110, 713–732 (1990).

    CAS PubMed  Google Scholar 

  19. 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).

    Article CAS PubMed PubMed Central  Google Scholar 

  20. Price, J. & Thurlow, L. Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer.Development104, 473–482 (1988).

    CAS PubMed  Google Scholar 

  21. 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).

    Article CAS PubMed PubMed Central  Google Scholar 

  22. 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).

    Article CAS PubMed PubMed Central  Google Scholar 

  23. Gray, G. E. & Sanes, J. R. Lineage of radial glia in the chicken optic tectum.Development114, 271–283 (1992).

    CAS PubMed  Google Scholar 

  24. Lewis, J. Notch signalling and the control of cell fate choices in vertebrates.Semin. Cell. Dev. Biol.9, 583–589 (1998).

    Article CAS PubMed  Google Scholar 

  25. 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.Development121, 3637–3650 (1995).

    CAS PubMed  Google Scholar 

  26. Gaiano, N., Nye, J. S. & Fishell, G. Radial glial identity is promoted by Notch1 signaling in the murine forebrain.Neuron26, 395–404 (2000).

    Article CAS PubMed  Google Scholar 

  27. 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).

    Article CAS PubMed PubMed Central  Google Scholar 

  28. Anderson, S. A., Eisenstat, D. D., Shi, L. & Rubenstein, J. Interneuron migration from basal forebrain to neocortex: dependence on dlx genes.Science278, 474–476 (1997).

    Article ADS CAS PubMed  Google Scholar 

  29. 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).

    Article CAS PubMed  Google Scholar 

  30. Blanton, M. G., LoTurco, J. J. & Kriegstein, A. R. Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex.J. Neurosci. Methods30, 203–210 (1989).

    Article CAS PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Departments of Neurology,

    Stephen C. Noctor, Alexander C. Flint & Arnold R. Kriegstein

  2. Departments of Pathology,

    Arnold R. Kriegstein

  3. Center for Neurobiology and Behavior, Columbia University College of Physicians & Surgeons, 630 West 168th Street, New York, 10032, New York, USA

    Tamily A. Weissman, Ryan S. Dammerman & Arnold R. Kriegstein

Authors
  1. Stephen C. Noctor
  2. Alexander C. Flint
  3. Tamily A. Weissman
  4. Ryan S. Dammerman
  5. Arnold R. Kriegstein

Corresponding author

Correspondence toArnold R. Kriegstein.

Rights and permissions

About this article

Cite this article

Noctor, S., Flint, A., Weissman, T.et al. Neurons derived from radial glial cells establish radial units in neocortex.Nature409, 714–720 (2001). https://doi.org/10.1038/35055553

Download citation

This article is cited by

Access through your institution
Buy or subscribe

Advertisement

Search

Advanced search

Quick links

Nature Briefing

Sign up for theNature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox.Sign up for Nature Briefing
[8]ページ先頭
©2009-2025 Movatter.jp