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Effects of Brn-4 on the neuronal differentiation of neural stem cells derived from rat midbrain

Authors

  • Xue-Feng Tan,

    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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  • Jian-Bing Qin,

    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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  • Guo-Hua Jin,

    Corresponding author
    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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  • Mei-Ling Tian,

    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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  • Hao-Ming Li,

    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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  • Hui-Xia Zhu,

    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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  • Xin-Hua Zhang,

    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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  • Jin-Hong Shi,

    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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  • Zhen Huang

    1. Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, Peoples Republic of China
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email jguohua@ntu.edu.cn

Abstract

NSCs (neural stem cells) provide a powerful research tool for the design and discovery of new approaches to cell replacement therapy during brain repair. However, the usefulness of this tool has been particulaly obstructed by limited neuronal differentiation of NSCs. Brn-4, a member of the POU domain family of transcription factors, has been previously implicated in the development of neurons by expression analysis. Here, we directly investigated the effects of Brn-4 on the neuronal differentiation and development of NSCs derived from the E13 rat midbrain. We found that Brn-4 knockdown in NSCs resulted in a significant decrease of MAP-2-positive neurons with immature morphology. Overexpression of Brn-4 in NSCs markedly increased the production and maturation of newborn neurons. These results suggest that Brn-4 has a critical role in the neuronal differentiation of mesencephalic NSCs and the maturation of newborn neurons. Brn-4 may be utilized to manipulate NSCs for gene and cell therapy of several neurological diseases.

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