A Genome-Wide Screen Reveals a Role for microRNA-1 in Modulating Cardiac Cell Polarity

Isabelle N. King, Li Qian, Jianping Liang, Yu Huang, Joseph T.C. Shieh, Chulan Kwon, Deepak Srivastava

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)497-510
Number of pages14
JournalDevelopmental Cell
Volume20
Issue number4
DOIs
StatePublished - Apr 19 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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