• Open Access

A Subpopulation of Individual Neural Progenitors in the Mammalian Dorsal Pallium Generates Both Projection Neurons and Interneurons In Vitro§

Authors

  • Yuqun Cai,

    1. Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People's Republic of China
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  • Yue Zhang,

    1. Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People's Republic of China
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  • Qin Shen,

    1. Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Center for Life Sciences, Tsinghua University, Beijing, People's Republic of China
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  • John L. R. Rubenstein,

    1. Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, California, USA
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  • Zhengang Yang

    Corresponding author
    1. Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People's Republic of China
    • Professor of Neuroscience, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, People's Republic of China
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    • Telephone: 86-21-54237872; Fax: 86-21-54237643


  • Abbreviations: IN, interneuron-like cells; PN, projection neuron-like cells.

  • Author contributions: Y.C.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; Y.Z.: conception and design, collection and assembly of data, and data analysis and interpretation; Q.S.: data analysis and interpretation; J.L.R.: data analysis and interpretation and manuscript writing; Z.Y.: conception and design, data analysis and interpretation, financial support, and manuscript writing. Y.C. and Y.Z. contributed equally to this work.

  • §

    Disclosure of potential conflicts of interest is found at the end of this article.

  • first published online in STEM CELLS EXPRESS February 4, 2013.

Abstract

There are two major classes of neurons in nervous systems: projection neurons and interneurons. During Drosophila nervous system development, a subpopulation of individual stem/progenitor cells gives rise to both motor neurons and interneurons. However, it remains unknown whether individual stem/progenitor cells in the mammalian brain also have the potential to give rise to both projection neurons and interneurons. Here we present evidence that single mouse neocortical progenitors generated both projection neurons and GABAergic interneurons based on studies using fluorescence-activated cell sorting (to obtain individual progenitors) and in vitro clonal analysis using time-lapse video microscopy and immunostaining. We determined that a subpopulation of individual dorsal pallial progenitors from E11.5 Dlx5/6-cre-IRES-EGFP and GAD67-GFP mice can generate both GFP-negative/Tbr1-positive (GFP/Tbr1+)/Tuj1+ cells and GFP+/Sp8+/calretinin+/Tuj1+ cells. The GFP/Tbr1+/Tuj1+ cells had morphological features of cultured projection neurons. Quantitative analysis of the reconstructed lineage trees derived from single progenitors showed that the projection neuron lineage appeared earlier than the interneuron lineage; however, more interneuron-like cells were produced than projection neuron-like cells. Thus, our results provide direct in vitro evidence that individual progenitors of the mammalian dorsal pallium can generate both projection neurons and interneurons. STEM Cells 2013;31:1139–1201

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