RAR[beta]2 expression is induced by the down-regulation of microRNA 133a during caudal spinal cord regeneration in the adult newt

Background: Adult urodele amphibians represent unique model organisms to study spinal cord regeneration. Trauma to the spinal cord induces an ependymal response, activating multipotent neural stem cells that contribute to the redifferentiation of both glia and neurons in the regenerate. The molecular events underlying this ependymal response are not completely understood, but likely involve coordinated global changes in gene expression. MicroRNAs and retinoid signaling are postulated to orchestrate these patterns of gene expression in response to trauma. Our objectives were to determine the roles played by some miRNAs as potential regulators of retinoid signaling in this process. Results: We found that the expression levels of miRNAs 133a, 203, and 124a are dysregulated during the first 21 days post amputation (dpa). Interestingly, these miRNAs are expressed primarily within the ependymoglia. We have shown in vitro that a miR-133a mimic targets the 3' UTR of the newt RAR[beta]2 transcript. Importantly, upregulation of this mimic in vivo led to a significant decline in RAR[beta]2 protein at 14 dpa and inhibited regeneration. Conclusions: These data are the first to link miRNAs and retinoid signaling during spinal cord regeneration and provide support for miR-133a as an upstream regulator of RAR[beta]2 expression in this process. Developmental Dynamics 243:1581-1590, 2014. © 2014 Wiley Periodicals, Inc. Key Findings This manuscript provides additional evidence for a critical role for retinoid signaling in ependymal cells during regeneration of the spinal cord in a regeneration-competent species, the adult newt First evidence for a specific miRNA (miR-133a) regulating RAR beta expression in vivo during adult newt spinal cord regeneration. In vitro evidence provided that miR-133a targets a specific sequence in the 3' UTR of the newt RAR beta transcript.