Abstract

The Drosophila heart, also referred to as the dorsal vessel, pumps the insect blood, the hemolymph. The bilateral heart primordia develop from the most dorsally located mesodermal cells, migrate coordinately, and fuse to form the cardiac tube. Though much simpler, the fruit fly heart displays several developmental and functional similarities to the vertebrate heart and, as we discuss here, represents an attractive model system for dissecting mechanisms of cardiac aging and heart failure and identifying genes causing congenital heart diseases. Fast imaging technologies allow for the characterization of heartbeat parameters in the adult fly and there is growing evidence that cardiac dysfunction in human diseases could be reproduced and analyzed in Drosophila, as discussed here for heart defects associated with the myotonic dystrophy type 1. Overall, the power of genetics and unsuspected conservation of genes and pathways puts Drosophila at the heart of fundamental and applied cardiac research.

Highlights

  • There is growing interest in using Drosophila to dissect molecular mechanisms of cardiac diseaseand aging-associated heart failure [43]. In this part of the review, we focus on the application of Drosophila to identifying new genes implicated in cardiac aging, heart failure, and in congenital heart diseases, and as an example, discuss how the fly model helps us gain an understanding of cardiac defects associated with myotonic dystrophy type 1 (DM1), a toxic transcript repeat disease

  • Deregulations of genes and pathways involved in cardiac aging such as Insulin Growth Factor (IGF) and the Target of Rapamycin (TOR) pathway [48,49], and genes encoding ion channels such as Ca/Calmodulin-dependent protein Kinase II (CaMKII) [50]

  • The Drosophila model has helped to identify novel genes and pathways involved in arrhythmias [47], atrial fibrillation [80], and channelopathies [81]

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Summary

Introduction

With its short life cycle (10 days at 25 ◦ C), high offspring numbers (2000 eggs per female), low maintenance costs, and conservation of genes and cellular pathways, Drosophila is an outstanding model for genetic studies. Drosophila counterparts, among which 26 were identified as associated with cardiovascular diseases [7]. Such conservation of genes, signaling pathways, and cellular processes, make the Drosophila cardiovascular system an amenable genetic model to study cardiac development, function, and diseases [8]. We discuss the mechanisms of Drosophila heart development and how this simple model is applied to the study of congenital heart diseases.

The Drosophila Heart
Cardiac Development in Embryos
Vertebrate Heart and Its Similarity with the Drosophila Cardiac Tube
Studying Cardiac Aging and Heart Failure in Drosophila
Identifying Genes Involved in Congenital Heart Defects
Modeling Myotonic Dystrophy Type 1 Heart Defects
Conclusions
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