microRNA-219 is highly expressed in the brain and spinal cord and its overexpression is necessary and sufficient to promote oligodendrocyte differentiation. It functions in part by directly repressing negative regulators of oligodendrocyte differentiation, including transcription factors Sox6 and Hes5. Additionally, microRNA-219 directly represses the expression of PDGFRalpha, FoxJ3, and ZFP238 proteins, all of which normally help to promote oligodendrocyte precursor cell proliferation.
microRNA-219 expression is partly controlled through the N-methyl-d-aspartate receptor (NMDAR) pathway. NMDAR activation selectively downregulates mature miR -219 levels and pharmacological blockade of N-methyl-d-aspartate receptor (NMDAR)-dependent LTP enhanced expression of mature microRNA-219.
- Zhao X, He X, Han X, Yu Y, Ye F, Chen Y, Hoang T, Xu X, Mi QS, Xin M, Wang F, Appel B, Lu QR. (2010) MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 65(5), 612-26. [abstract]
- Wibrand K, Panja D, Tiron A, Ofte ML, Skaftnesmo KO, Lee CS, Pena JT, Tuschl T, Bramham CR. (2010) Differential regulation of mature and precursor microRNA expression by NMDA and metabotropic glutamate receptor activation during LTP in the adult dentate gyrus in vivo. Eur J Neurosci (4), 636-45 [abstract]