TISSUE-SPECIFIC STEM CELLS MicroRNA miR-137 Regulates Neuronal Maturation by Targeting

The maturation of young neurons is regulated by complex mechanisms and dysregulation of this process is frequently found in neurodevepmental disorders. MicroRNAs have been implicated in several steps of neuronal maturation including dendritic and axonal growth, spine development, and synapto-genesis. We demonstrate that one brain-enriched microRNA, miR-137, has a significant role in regulating neuronal matura-tion. Overexpression of miR-137 inhibits dendritic morpho-genesis, phenotypic maturation, and spine development both in brain and cultured primary neurons. On the other hand, a reduction in miR-137 had opposite effects. We further show that miR-137 targets the Mind bomb one (Mib1) protein through the conserved target site located in the 30 untranslated region of Mib1 messenger RNA. Mib1 is an ubiquitin ligase known to be important for neurodevelopment. We show that exogenously expressedMib1 could partially rescue the pheno-types associated with miR-137 overexpression. These results demonstrate a novel miRNA-mediated mechanism involving miR-137 andMib1 that function to regulate neuronal matura-tion and dendritic morphogenesis during development. STEM CELLS 2010;28:1060–1070 Disclosure of potential conflicts of interest is found at the end of this article