Increasing Doublecortin Expression Promotes Migration of Human Embryonic Stem Cell-Derived Neurons

Authors

  • Radmila Filipovic,

    Corresponding author
    1. Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA
    • Department of Physiology and Neurobiology, University of Connecticut, Storrs 06268, Connecticut, USA
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    • Author contributions: J.L.: conception and design, data analysis and interpretation, manuscript writing, financial support, and final approval of manuscript.; R.F.: conception and design, collection and/or assembly of data, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript; S.S.K.: collection and assembly of data; C.F.: plasmid construction.

    • Telephone: 1-860-48703283; Fax: 1-860-486-3033

  • Saranya Santhosh Kumar,

    1. Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA
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    • Author contributions: J.L.: conception and design, data analysis and interpretation, manuscript writing, financial support, and final approval of manuscript.; R.F.: conception and design, collection and/or assembly of data, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript; S.S.K.: collection and assembly of data; C.F.: plasmid construction.

  • Chris Fiondella,

    1. Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA
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    • Author contributions: J.L.: conception and design, data analysis and interpretation, manuscript writing, financial support, and final approval of manuscript.; R.F.: conception and design, collection and/or assembly of data, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript; S.S.K.: collection and assembly of data; C.F.: plasmid construction.

  • Joseph Loturco

    1. Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA
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    • Author contributions: J.L.: conception and design, data analysis and interpretation, manuscript writing, financial support, and final approval of manuscript.; R.F.: conception and design, collection and/or assembly of data, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript; S.S.K.: collection and assembly of data; C.F.: plasmid construction.


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

  • First published online in STEM CELLSEXPRESS June 31, 2012.

Abstract

Human embryonic stem cell-derived neuronal progenitors (hNPs) provide a potential source for cellular replacement following neurodegenerative diseases. One of the greatest challenges for future neuron replacement therapies will be to control extensive cell proliferation and stimulate cell migration of transplanted cells. The doublecortin (DCX) gene encodes the protein DCX, a microtubule-associated protein essential for the migration of neurons in the human brain. In this study, we tested whether increasing the expression of DCX in hNPs would favorably alter their proliferation and migration. Migration and proliferation of hNPs was compared between hNPs expressing a bicistronic DCX/IRES-GFP transgene and those expressing a green fluorescent protein (GFP) transgene introduced by piggyBac-mediated transposition. The DCX-transfected hNPs showed a significant decrease in their proliferation and migrated significantly further on two different substrates, Matrigel and brain slices. Additionally, a dense network of nestin-positive (+) and vimentin+ fibers were found to extend from neurospheres transplanted onto brain slices, and this fiber growth was increased from neurospheres containing DCX-transfected hNPs. In summary, our results show that increased DCX expression inhibits proliferation and promotes migration of hNPs. Stem Cells2012;30:1852–1862

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