Drosophila mir-9a regulates wing development via fine-tuning expression of the LIM only factor, dLMO.

MicroRNAs are short non-coding endogenous RNAs that are implicated in regulating various aspects of plants and animal development, however their functions in organogenesis are largely unknown. Here we report that mir-9a belonging to the mir-9 family, regulates Drosophila wing development through a functional target site in the 3' untranslated region of the Drosophila LIM only protein, dLMO. dLMO is a transcription cofactor, that directly inhibits the activity of Apterous, the LIM-HD factor required for the proper dorsal identity of the wings. Deletions of the 3' untranslated region, including the mir-9a site, generate gain-of-function dLMO mutants (Beadex) associated with high levels of dLMO mRNA and protein. Beadex mutants lack wing margins, a phenotype also observed in null mir-9a mutants. We found that mir-9a and dLMO are co-expressed in wing discs and interact genetically for controlling wing development. Lack of mir-9a results in overexpression of dLMO, while gain-of-function mir-9a mutant suppresses dLMO expression. These data indicate that a function of mir-9a is to ensure the appropriate stoichiometry of dLMO during Drosophila wing development. The mir-9a binding site is conserved in the human counterpart LMO2, the T-cell acute leukemia oncogene, suggesting that mir-9 might apply a similar strategy to maintain LMO2 expression under a detrimental threshold.