Developmental Cell
Volume 20, Issue 4, 19 April 2011, Pages 497-510
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Article
A Genome-Wide Screen Reveals a Role for microRNA-1 in Modulating Cardiac Cell Polarity

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Summary

Many molecular pathways involved in heart disease have their roots in evolutionarily ancient developmental programs that depend critically on gene dosage and timing. MicroRNAs (miRNAs) modulate gene dosage posttranscriptionally, and among these, the muscle-specific miR-1 is particularly important for developing and maintaining somatic/skeletal and cardiac muscle. To identify pathways regulated by miR-1, we performed a forward genetic screen in Drosophila using wing-vein patterning as a biological assay. We identified several unexpected genes that genetically interacted with dmiR-1, one of which was kayak, encodes a developmentally regulated transcription factor. Additional studies directed at this genetic relationship revealed a previously unappreciated function of dmiR-1 in regulating the polarity of cardiac progenitor cells. The mammalian ortholog of kayak, c-Fos, was dysregulated in hearts of gain- or loss-of-function miR-1 mutant mice in a stress-dependent manner. These findings illustrate the power of Drosophila-based screens to find points of intersection between miRNAs and conserved pathways in mammals.

Highlights

► A genome-wide screen in Drosophila revealed that dmiR-1 directly targets kayakdmiR-1 modulation of kayak contributes to normal cell polarity in the fly heart ► miR-1 limits the induction of c-Fos, during the mammalian cardiac stress response

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These authors contributed equally to the work