Inhibition of miR-15a Promotes BDNF Expression and Rescues Dendritic Maturation Deficits in MeCP2-Deficient Neurons

Stem Cells. 2015 May;33(5):1618-29. doi: 10.1002/stem.1950.


In both the embryonic and adult brain, a critical step in neurogenesis is neuronal maturation. Deficiency of MeCP2 leads to Rett syndrome, a severe neurodevelopmental disorder. We have previously shown that MeCP2 plays critical roles in the maturation step of new neurons during neurogenesis. MeCP2 is known to regulate the expression of brain-derived neurotrophic factor (BDNF), a potent neurotrophic factor for neuronal maturation. Nevertheless, how MeCP2 regulates BDNF expression and how MeCP2 deficiency leads to reduced BDNF expression remain unclear. Here, we show that MeCP2 regulates the expression of a microRNA, miR-15a. We find that miR-15a plays a significant role in the regulation of neuronal maturation. Overexpression of miR-15a inhibits dendritic morphogenesis in immature neurons. Conversely, a reduction in miR-15a has the opposite effect. We further show that miR-15a regulates expression levels of BDNF, and exogenous BDNF could partially rescue the neuronal maturation deficits resulting from miR-15a overexpression. Finally, inhibition of miR-15a could rescue neuronal maturation deficits in MeCP2-deficient adult-born new neurons. These results demonstrate a novel role for miR-15a in neuronal development and provide a missing link in the regulation of BDNF by MeCP2.

Keywords: MeCP2; Neuron; Rett syndrome; dendrite; miRNA; neuronal Maturation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Differentiation / genetics
  • Dendrites / metabolism*
  • Gene Expression Regulation
  • Hippocampus / pathology
  • Male
  • Methyl-CpG-Binding Protein 2 / deficiency*
  • Methyl-CpG-Binding Protein 2 / metabolism
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Models, Biological
  • Mutation / genetics


  • Brain-Derived Neurotrophic Factor
  • Methyl-CpG-Binding Protein 2
  • MicroRNAs
  • Mirn15 microRNA, mouse