title: A genome-wide screen reveals a role for microRNA-1 in modulating cardiac cell polarity.
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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA. iking@gladstone.ucsf.edu
authors.forename: Isabelle N
authors.initials: IN
authors.lastname: King
authors.forename: Li
authors.initials: L
authors.lastname: Qian
authors.forename: Jianping
authors.initials: J
authors.lastname: Liang
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Joseph T C
authors.initials: JT
authors.lastname: Shieh
authors.forename: Chulan
authors.initials: C
authors.lastname: Kwon
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics* / Q000502:physiology; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D055106:Genome-Wide Association Study; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000166:cytology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger