title: MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling.
abstract: MicroRNAs (miRNAs) are genomically encoded small RNAs that hybridize with messenger RNAs, resulting in degradation or translational inhibition of targeted transcripts. The potential for miRNAs to regulate cell-lineage determination or differentiation from pluripotent progenitor or stem cells is unknown. Here, we show that microRNA1 (miR-1) is an ancient muscle-specific gene conserved in sequence and expression in Drosophila. Drosophila miR-1 (dmiR-1) is regulated through a serum response factor-like binding site in cardiac progenitor cells. Loss- and gain-of-function studies demonstrated a role for dmiR-1 in modulating cardiogenesis and in maintenance of muscle-gene expression. We provide in vivo evidence that dmiR-1 targets transcripts encoding the Notch ligand Delta, providing a potential mechanism for the expansion of cardiac and muscle progenitor cells and failure of progenitor cell differentiation in some dmiR-1 mutants. These findings demonstrate that dmiR-1 may "fine-tune" critical steps involved in differentiation of cardiac and somatic muscle progenitors and targets a pathway required for progenitor cell specification and asymmetric cell division.
authors.affiliation: Gladstone Institute of Cardiovascular Disease and Department of Pediatrics, University of California, 1650 Owens Street, San Francisco, CA 94158.
authors.forename: Chulan
authors.initials: C
authors.lastname: Kwon
authors.forename: Zhe
authors.initials: Z
authors.lastname: Han
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D011995:Recombination, Genetic; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D014162:Transfection; D019076:Transgenes; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D051880:Receptors, Notch; C064045:delta protein; D049452:Green Fluorescent Proteins