Drosophila miR-9a Targets the ECM Receptor Dystroglycan to Canalize Myotendinous Junction Formation

• miR-9a targets muscle genes to abolish their aberrant transcription in tendons
• miR-9a and Dg embryonic expression patterns are dynamic and mutually exclusive
• miR-9a targeting of Dg in pretendons is key for accurate myotendinous attachment
• Dg establishes a specific ECM gradient that influences muscle-tendon signaling

SummaryEstablishment of intercellular interactions between various cell types of different origin is vital for organism development and tissue maintenance. Therefore, precise timing, expression pattern, and amounts of extracellular matrix (ECM) proteins must be tightly regulated. Particularly, the ECM is important for the development and function of myotendinous junctions (MTJs). We find that precise levels of the ECM receptor Dystroglycan (Dg) are required for MTJ formation in Drosophila and that Dg levels in this process are controlled by miR-9a. In the embryo, Dg is enriched at the termini of the growing muscles facing the tendon matrix and absent from miR-9a-expressing tendons. This gradient of Dg expression is crucial for proper muscle-tendon attachments and is adjusted by miR-9a. In addition to Dg, miR-9a regulates the expression of several other critical muscle genes, and we therefore propose that during embryogenesis, miR-9a specifically controls the expression of mesodermal genes to canalize MTJ morphogenesis.

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