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

Abstract

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.

MiR-2 family regulates insect metamorphosis by controlling the juvenile hormone signaling pathway

“…A number of reports support this hypothesis; for example, during adult morphogenesis of D. melanogaster, let-7 is required for neuromusculature remodeling (16), whereas let-7 and miR-125 are needed for proper timing in the wing cell cycle and for the maturation of neuromuscular junctions (14). Also in D. melanogaster, iab-4 attenuates Ultrabithorax expression and causes a transformation of halteres to wings (15), whereas miR-9a contributes to wing development by modulating the expression of the transcription factor dLMO, which represses Apterous, a factor required for the proper dorsal identity of the wings (13). Specific miRNA functions in wing development have also been described in hemimetabolan species such as B. germanica, where depletion of let-7 and associated miRNAs affects vein patterning (27).…”

“…Only a few published studies had considered the contribution of miRNAs to this process, but these focused on specific aspects, such as wing formation and neuromuscular development (13)(14)(15)(16). They also used the fly Drosophila melanogaster as a model, a species that follows the holometabolan mode of metamorphosis, in which the juvenile stages are extremely divergent from the adult body plan and thus require a dramatic transformation for adult morphogenesis (17)(18)(19)(20).…”

Differential expression of miRNAs related to caste differentiation in the honey bee, Apis mellifera

“…The microRNA bantam regulates cell growth and proliferation, organ and body size, and germ cell fate (Brennecke et al 2003;Hipfner et al 2002;Moberg and Hariharan 2003;Yang et al 2009). The miR-210 is involved in the production and development of Drosophila ovaries and female gametes (Grun et al 2005), and miR-9a strongly influences wing development (Biryukova et al 2009).…”

Les multiples facettes d’un petit régulateur

“…SYNTHÈSE REVUES ou de l'adulte [14][15][16]. Les soies se forment à partir de la division d'une cellule progénitrice neurale appelée SOP (sensory organ precursor).…”

“…miR-9a, qui est présent dans toutes les cellules de l'ectoderme à l'exception des cellules SOP, semble agir à ces deux étapes. En effet, il inhibe dLMO (drosophila LIM only) qui participe à l'induction des facteurs proneuraux [14,15]. D'autre part, miR-9a inhibe, dans les cellules non SOP, l'expression du gène proneural sens (senseless) qui définit l'identité de la cellule SOP [16].…”