In a Drosophila screen for microRNAs with functional roles in the nervous system, mutations affecting mir-bft (mir-263a) were observed to exhibit a progressive locomotor climbing defect. It was determined that bft is expressed in glial cells and that mir-bft mutants also exhibit a glial phenotype: excitotoxic death of a subset of astrocyte-like and ensheathing glia in the CNS is observed.
Three genes encoding ionotropic glutamate receptors, Grik, Nmdar1, and Nmdar2, were identified as candidate targets of mir-bft. Since expression levels of miRNA targets are expected to be upregulated in miRNA mutants, the effect of RNAi-mediated knockdown of each of these genes was assessed in the bft mutant background. In each case, the climbing defect of mir-bft mutant animals was suppressed.
There are a large number of ionotropic glutamate receptors in both species. See Glutamate Ionotropic Receptors gene group reports at FlyBase (FBgg0000176) and at HGNC (https://www.genenames.org/data/genegroup/#!/group/284).
A similar system has been characterized in human, involving neural rather than glial expression of a microRNA that mediates ionotropic glutamate receptor levels (Harraz, 2012, pubmed:23112146).
[updated May 2019 by FlyBase; FBrf0222196]
Elevated concentrations of extracellular glutamate, released as a result of neural injury, are toxic to neurons. (Glutamate, NCBI Bookshelf, https://www.ncbi.nlm.nih.gov/books/NBK10807/)
Glutamate is generally acknowledged to be the most important transmitter for normal brain function. Nearly all excitatory neurons in the central nervous system are glutamatergic, and it is estimated that over half of all brain synapses release this agent. (Glutamate, NCBI Bookshelf, https://www.ncbi.nlm.nih.gov/books/NBK10807/)
The bft/mir-263a 23-nt mature microRNA is similar to the human MIR183 microRNA (FBrf0242402, FBrf0234481).
