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Mitotic spindle orientation predicts outer radial glial cell generation in human neocortex

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  • Bridget E. LaMonica

    (University of California, San Francisco, 35 Medical Center Way
    Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way
    Neuroscience Graduate Program, University of California, San Francisco, 1550 4th Street)

  • Jan H. Lui

    (University of California, San Francisco, 35 Medical Center Way
    Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way)

  • David V. Hansen

    (University of California, San Francisco, 35 Medical Center Way
    Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way
    Present address: Department of Neuroscience, Genentech, Inc., South San Francisco, California 94403, USA)

  • Arnold R. Kriegstein

    (University of California, San Francisco, 35 Medical Center Way
    Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way)

Abstract

The human neocortex is increased in size and complexity as compared with most other species. Neocortical expansion has recently been attributed to protracted neurogenesis by outer radial glial cells in the outer subventricular zone, a region present in humans but not in rodents. The mechanisms of human outer radial glial cell generation are unknown, but are proposed to involve division of ventricular radial glial cells; neural stem cells present in all developing mammals. Here we show that human ventricular radial glial cells produce outer radial glial cells and seed formation of the outer subventricular zone via horizontal divisions, which occur more frequently in humans than in rodents. We further find that outer radial glial cell mitotic behaviour is cell intrinsic, and that the basal fibre, inherited by outer radial glial cells after ventricular radial glial division, determines cleavage angle. Our results suggest that altered regulation of mitotic spindle orientation increased outer radial glial cell number, and ultimately neuronal number, during human brain evolution.

Suggested Citation

  • Bridget E. LaMonica & Jan H. Lui & David V. Hansen & Arnold R. Kriegstein, 2013. "Mitotic spindle orientation predicts outer radial glial cell generation in human neocortex," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2647
    DOI: 10.1038/ncomms2647
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