A Genome-wide Screen Reveals a Role for MicroRNA-1 in Modulating Cardiac Cell Polarity

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2011 Apr 19

PMID 21497762

Citations 13

Authors

Isabelle N King

Li Qian

Jianping Liang

Yu Huang

Joseph T C Shieh

Chulan Kwon

Deepak Srivastava

Affiliations

Soon will be listed here.

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.

Citing Articles

Transcription of microRNAs is regulated by developmental signaling pathways and transcription factors.

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The E3 ubiquitin ligase Nedd4/Nedd4L is directly regulated by microRNA 1.

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A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs.

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MicroRNAs and Cardiac Regeneration.

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References

Ryder E, Ashburner M, Bautista-Llacer R, Drummond J, Webster J, Johnson G . The DrosDel deletion collection: a Drosophila genomewide chromosomal deficiency resource. Genetics. 2007; 177(1):615-29. PMC: 2013729. DOI: 10.1534/genetics.107.076216. View

Zhao Y, Ransom J, Li A, Vedantham V, von Drehle M, Muth A . Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell. 2007; 129(2):303-17. DOI: 10.1016/j.cell.2007.03.030. View

Garcia-Bellido A, Cortes F, Milan M . Cell interactions in the control of size in Drosophila wings. Proc Natl Acad Sci U S A. 1994; 91(21):10222-6. PMC: 44990. DOI: 10.1073/pnas.91.21.10222. View

Frasch M, Hoey T, Rushlow C, Doyle H, Levine M . Characterization and localization of the even-skipped protein of Drosophila. EMBO J. 1987; 6(3):749-59. PMC: 553460. DOI: 10.1002/j.1460-2075.1987.tb04817.x. View

Ciapponi L, Jackson D, Mlodzik M, Bohmann D . Drosophila Fos mediates ERK and JNK signals via distinct phosphorylation sites. Genes Dev. 2001; 15(12):1540-53. PMC: 312716. DOI: 10.1101/gad.886301. View

Ivey K, Muth A, Arnold J, King F, Yeh R, Fish J . MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell. 2008; 2(3):219-29. PMC: 2293325. DOI: 10.1016/j.stem.2008.01.016. View

Chen J, Mandel E, Thomson J, Wu Q, Callis T, Hammond S . The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2005; 38(2):228-33. PMC: 2538576. DOI: 10.1038/ng1725. View

Wallingford J, Fraser S, Harland R . Convergent extension: the molecular control of polarized cell movement during embryonic development. Dev Cell. 2002; 2(6):695-706. DOI: 10.1016/s1534-5807(02)00197-1. View

Larsen T, Skar R, Frotjold E, Haukanes K, Greve G, Saetersdal T . Regional activation of the immediate-early response gene c-fos in infarcted rat hearts. Int J Exp Pathol. 1998; 79(3):163-72. PMC: 3220382. DOI: 10.1046/j.1365-2613.1998.00062.x. View

10.

Kwon C, Han Z, Olson E, Srivastava D . MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci U S A. 2005; 102(52):18986-91. PMC: 1315275. DOI: 10.1073/pnas.0509535102. View

11.

Ramirez M, Sah V, Zhao X, Hunter J, Chien K, Brown J . The MEKK-JNK pathway is stimulated by alpha1-adrenergic receptor and ras activation and is associated with in vitro and in vivo cardiac hypertrophy. J Biol Chem. 1997; 272(22):14057-61. DOI: 10.1074/jbc.272.22.14057. View

12.

Cavigelli M, Dolfi F, Claret F, Karin M . Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. EMBO J. 1995; 14(23):5957-64. PMC: 394715. DOI: 10.1002/j.1460-2075.1995.tb00284.x. View

13.

Costantini D, Arruda E, Agarwal P, Kim K, Zhu Y, Zhu W . The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell. 2005; 123(2):347-58. PMC: 1480411. DOI: 10.1016/j.cell.2005.08.004. View

14.

Zallen J . Planar polarity and tissue morphogenesis. Cell. 2007; 129(6):1051-63. DOI: 10.1016/j.cell.2007.05.050. View

15.

MacMullin A, Jacobs J . Slit coordinates cardiac morphogenesis in Drosophila. Dev Biol. 2006; 293(1):154-64. DOI: 10.1016/j.ydbio.2006.01.027. View

16.

Santiago-Martinez E, Soplop N, Kramer S . Lateral positioning at the dorsal midline: Slit and Roundabout receptors guide Drosophila heart cell migration. Proc Natl Acad Sci U S A. 2006; 103(33):12441-6. PMC: 1567898. DOI: 10.1073/pnas.0605284103. View

17.

Classen A, Anderson K, Marois E, Eaton S . Hexagonal packing of Drosophila wing epithelial cells by the planar cell polarity pathway. Dev Cell. 2005; 9(6):805-17. DOI: 10.1016/j.devcel.2005.10.016. View

18.

Phillips H, Rhee H, Murdoch J, Hildreth V, Peat J, Anderson R . Disruption of planar cell polarity signaling results in congenital heart defects and cardiomyopathy attributable to early cardiomyocyte disorganization. Circ Res. 2007; 101(2):137-45. DOI: 10.1161/CIRCRESAHA.106.142406. View

19.

Han Z, Fujioka M, Su M, Liu M, Jaynes J, Bodmer R . Transcriptional integration of competence modulated by mutual repression generates cell-type specificity within the cardiogenic mesoderm. Dev Biol. 2002; 252(2):225-40. PMC: 2693947. DOI: 10.1006/dbio.2002.0846. View

20.

Cooper M, Bray S . Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. Nature. 1999; 397(6719):526-30. DOI: 10.1038/17395. View