Expression of Neurogenin 1 in Mouse Embryonic Stem Cells Directs the Differentiation of Neuronal Precursors and Identifies Unique Patterns of Down-stream Gene Expression

Authors

  • J. Matthew Velkey,

    1. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan
    2. Department of Cell Biology, Duke University, Durham, North Carolina
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  • K. Sue O'Shea

    Corresponding author
    • Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan
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Correspondence to: K.S. O'Shea, Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, 3051 BSRB, Ann Arbor, MI 48109-2200. E-mail: oshea@umich.edu

Abstract

Background: Delineating the cascades of growth and transcription factor expression that shape the developing nervous system will improve our understanding of its molecular histogenesis and suggest strategies for cell replacement therapies. In the current investigation, we examined the ability of the proneural gene, Neurogenin1 (Neurog1; also Ngn1, Neurod3), to drive differentiation of pluripotent embryonic stem cells (ESC). Results: Transient expression of Neurog1 in ESC was sufficient to initiate neuronal differentiation, and produced neuronal subtypes reflecting its expression pattern in vivo. To begin to address the molecular mechanisms involved, we used microarray analysis to identify potential down-stream targets of Neurog1 expressed at sequential stages of neuronal differentiation. Conclusions: ESC expressing Neurogenin1 begin to withdraw from cycle and form precursors that differentiate exclusively into neurons. This work identifies unique patterns of gene expression following expression of Neurog1, including genes and signaling pathways involved in process outgrowth and cell migration, regional differentiation of the nervous system, and cell cycle. Developmental Dynamics 242:230–253, 2013. © 2013 Wiley Periodicals, Inc.

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