Regulatory potential and developmental function of Drosophila melanogaster microRNA-315

MicroRNAs exist as a large family of small, non-coding RNAs, 21-23 nucleotides in length, that have gained prominence over the last decade due to their ability to repress expression of a large repertoire of target genes. To better understand the regulatory capacity of specific miRNAs, over-expression studies were carried out in multiple Drosophila tissues at different developmental stages. From these studies, mir-315 was noted for its ability to induce transdifferentiation of notum tissue into an ectopic pair of fully patterned wings. This transformation is joined by the observation that miR-315 targets two inhibitors of Wingless signaling, axin and Notum. Mir-315 over-expression phenotypes can be rescued by increasing the dosage of either target, indicating a genetic interaction between the miRNA and these two targets. These data indicate that signaling pathways, such as the Wg pathway, represent an ideal setting in which miRNA regulation might be employed to regulate output.;Mir-315 is endogenously expressed in the developing CNS of Drosophila embryos where it colocalizes with neuroblast marker genes castor and pdm/nubbin. The expression in neural lineages is controlled largely by two well-conserved enhancer elements. Loss of mir-315 by genetic deletion results in lethality at larval stages that is accompanied by locomotion defects and aberrant synapse morphology. Lethality is partially rescued by modifying gene dosage for the validated target Notum while synapse morphology and locomotion defects appear to be most sensitive to gene dosage for frazzled, another validated miR-315 target. Taken together, these data support a model in which multiple miR-315 targets contribute to various aspects of the mutant phenotype and set the stage for future studies of mir-315 function in the nervous system.