title: MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish.
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.
authors: W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors: Young-Mi
authors: YM
authors: Yu
authors: Kurt M
authors: KM
authors: Gibbs
authors: Jonathan
authors: J
authors: Davila
authors: Neil
authors: N
authors: Campbell
authors: Simon
authors: S
authors: Sung
authors: Tihomira I
authors: TI
authors: Todorova
authors: Seiji
authors: S
authors: Otsuka
authors: Hatem E
authors: HE
authors: Sabaawy
authors: Ronald P
authors: RP
authors: Hart
authors: Melitta
authors: M
authors: Schachner
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function; D013116:Spinal Cord / Q000473:pathology / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D058630:Spinal Cord Regeneration / Q000502:physiology*; D015027:Zebrafish / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C553925:MIRN133 microRNA, zebrafish; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D020742:rhoA GTP-Binding Protein