MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish.
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MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish. / Yu, Young-Mi; Gibbs, Kurt M; Davila, Jonathan; Campbell, Neil; Sung, Simon; Todorova, Tihomira I; Otsuka, Seiji; Sabaawy, Hatem E; Hart, Ronald P; Schachner, Melitta.
In: EUR J NEUROSCI, Vol. 33, No. 9, 9, 2011, p. 1587-1597.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish.
AU - Yu, Young-Mi
AU - Gibbs, Kurt M
AU - Davila, Jonathan
AU - Campbell, Neil
AU - Sung, Simon
AU - Todorova, Tihomira I
AU - Otsuka, Seiji
AU - Sabaawy, Hatem E
AU - Hart, Ronald P
AU - Schachner, Melitta
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Motor Activity/physiology
KW - MicroRNAs/genetics/metabolism
KW - Spinal Cord Injuries/physiopathology
KW - Brain/physiology
KW - Oligonucleotides, Antisense/genetics/metabolism
KW - Recovery of Function
KW - Spinal Cord/pathology/physiology
KW - Spinal Cord Regeneration/physiology
KW - Zebrafish/physiology
KW - rhoA GTP-Binding Protein/genetics/metabolism
KW - Animals
KW - Motor Activity/physiology
KW - MicroRNAs/genetics/metabolism
KW - Spinal Cord Injuries/physiopathology
KW - Brain/physiology
KW - Oligonucleotides, Antisense/genetics/metabolism
KW - Recovery of Function
KW - Spinal Cord/pathology/physiology
KW - Spinal Cord Regeneration/physiology
KW - Zebrafish/physiology
KW - rhoA GTP-Binding Protein/genetics/metabolism
M3 - SCORING: Journal article
VL - 33
SP - 1587
EP - 1597
JO - EUR J NEUROSCI
JF - EUR J NEUROSCI
SN - 0953-816X
IS - 9
M1 - 9
ER -
