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Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand.

Publication ,  Journal Article
Kim, I-M; Wolf, MJ; Rockman, HA
Published in: Circ Res
April 16, 2010

RATIONALE: Drosophila has been recognized as a model to study human cardiac diseases. OBJECTIVE: Despite these findings, and the wealth of tools that are available to the fly community, forward genetic screens for adult heart phenotypes have been rarely performed because of the difficulty in accurately measuring cardiac function in adult Drosophila. METHODS AND RESULTS: Using optical coherence tomography to obtain real-time analysis of cardiac function in awake Drosophila, we performed a genomic deficiency screen in adult flies. Based on multiple complementary approaches, we identified CG31665 as a novel gene causing dilated cardiomyopathy. CG31665, which we name weary (wry), has structural similarities to members of the Notch family. Using cell aggregation assays and gamma-secretase inhibitors we show that Wry is a novel Notch ligand that can mediate cellular adhesion with Notch expressing cells and transactivates Notch to promote signaling and nuclear transcription. Importantly, Wry lacks a DSL (Delta-Serrate-Lag) domain that is common feature to the other Drosophila Notch ligands. We further show that Notch signaling is critically important for the maintenance of normal heart function of the adult fly. CONCLUSIONS: In conclusion, we identify a previously unknown Notch ligand in Drosophila that when deleted causes cardiomyopathy. Our study suggests that Notch signaling components may be a therapeutic target for dilated cardiomyopathy.

Duke Scholars

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

April 16, 2010

Volume

106

Issue

7

Start / End Page

1233 / 1243

Location

United States

Related Subject Headings

  • Transfection
  • Transcriptional Activation
  • Tomography, Optical Coherence
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Notch
  • RNA Interference
  • Promoter Regions, Genetic
  • Phenotype
  • Ligands
 

Citation

APA
Chicago
ICMJE
MLA
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Kim, I.-M., Wolf, M. J., & Rockman, H. A. (2010). Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand. Circ Res, 106(7), 1233–1243. https://doi.org/10.1161/CIRCRESAHA.109.213785
Kim, Il-Man, Matthew J. Wolf, and Howard A. Rockman. “Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand.Circ Res 106, no. 7 (April 16, 2010): 1233–43. https://doi.org/10.1161/CIRCRESAHA.109.213785.
Kim I-M, Wolf MJ, Rockman HA. Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand. Circ Res. 2010 Apr 16;106(7):1233–43.
Kim, Il-Man, et al. “Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand.Circ Res, vol. 106, no. 7, Apr. 2010, pp. 1233–43. Pubmed, doi:10.1161/CIRCRESAHA.109.213785.
Kim I-M, Wolf MJ, Rockman HA. Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand. Circ Res. 2010 Apr 16;106(7):1233–1243.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

April 16, 2010

Volume

106

Issue

7

Start / End Page

1233 / 1243

Location

United States

Related Subject Headings

  • Transfection
  • Transcriptional Activation
  • Tomography, Optical Coherence
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Notch
  • RNA Interference
  • Promoter Regions, Genetic
  • Phenotype
  • Ligands