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

Inna Biryukova, Joëlle Asmar, Houari Abdesselem, Pascal Heitzler

Department of Cell and Developmental Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.

Developmental biology 2009 Mar 15

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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.

Citation

Inna Biryukova, Joëlle Asmar, Houari Abdesselem, Pascal Heitzler. Drosophila mir-9a regulates wing development via fine-tuning expression of the LIM only factor, dLMO. Developmental biology. 2009 Mar 15;327(2):487-96