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MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish

Authors

  • Young-Mi Yu,

    1. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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    • Authors contributed equally to this work.

  • Kurt M. Gibbs,

    1. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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    • Authors contributed equally to this work.

  • Jonathan Davila,

    1. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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  • Neil Campbell,

    1. The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA
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  • Simon Sung,

    1. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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  • Tihomira I. Todorova,

    1. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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  • Seiji Otsuka,

    1. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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  • Hatem E. Sabaawy,

    1. The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA
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  • Ronald P. Hart,

    1. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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  • Melitta Schachner

    1. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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M. Schachner, as above.
E-mail: schachner@biology.rutgers.edu

Abstract

MicroRNAs (miRNAs) play important roles during development and also in adult organisms by regulating the expression of multiple target genes. Here, we studied the function of miR-133b during zebrafish spinal cord regeneration and show upregulation of miR-133b expression in regenerating neurons of the brainstem after transection of the spinal cord. miR-133b has been shown to promote tissue regeneration in other tissue, but its ability to do so in the nervous system has yet to be tested. Inhibition of miR-133b expression by antisense morpholino (MO) application resulted in impaired locomotor recovery and reduced regeneration of axons from neurons in the nucleus of the medial longitudinal fascicle, superior reticular formation and intermediate reticular formation. miR-133b targets the small GTPase RhoA, which is an inhibitor of axonal growth, as well as other neurite outgrowth-related molecules. Our results indicate that miR-133b is an important determinant in spinal cord regeneration of adult zebrafish through reduction in RhoA protein levels by direct interaction with its mRNA. While RhoA has been studied as a therapeutic target in spinal cord injury, this is the first demonstration of endogenous regulation of RhoA by a microRNA that is required for spinal cord regeneration in zebrafish. The ability of miR-133b to suppress molecules that inhibit axon regrowth may underlie the capacity for adult zebrafish to recover locomotor function after spinal cord injury.

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