Drosophila microRNA-9a modulates the process of muscle attachment assembly via downregulation of Dystroglycan. Andriy S. Yatsenko, Halyna R. Shcherbata. MPRG Gene Expression and Signaling, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany.

   Coordinated transcription factor networks are prominent regulators of cell fate during embryonic development and adult life. Now it is becoming evident that in conjunction with transcription factors at least three epigenetic elements (chromatin structure, DNA methylation, and microRNAs) help to form a reciprocal regulatory circuit to maintain cell identity and differentiation. miRNAs, based on their paradoxical properties, e.g., being highly evolutionarily conserved but not essential, have been proposed to play a role in generating biological robustness as canalization factors to buffer gene expression against perturbation or variability. We identified new roles for the ECM receptor Dystroglycan and miR-9a in establishment of muscle-tendon connections. Dystroglycan is specifically enriched at the termini of the growing muscles facing the tendon matrix and absent from tendons. This differential localization is crucial for proper muscle-tendon attachments and is adjusted by miR-9a. Interestingly, various critical genes required for muscle development are putative miR-9a targets and miR-9a is expressed in non-mesodermal cells. Since exogenous expression of miR-9a in mesoderm completely abolishes muscle formation, we hypothesize that miR-9a acts as a guardian to prevent noisy muscle gene expression in the epidermal tendon precursor cells that can be challenged upon stress or transcriptional noise.