A new method for detection and quantification of heartbeat parameters in Drosophila, zebrafish, and embryonic mouse hearts.

The genetic basis of heart development is remarkably conserved from Drosophila to mammals, and insights from flies have greatly informed our understanding of vertebrate heart development. Recent evidence suggests that many aspects of heart function are also conserved and the genes involved in heart development also play roles in adult heart function. We have developed a Drosophila heart preparation and movement analysis algorithm that allows quantification of functional parameters. Our methodology combines high-speed optical recording of beating hearts with a robust, semi-automated analysis to accurately detect and quantify, on a beat-to-beat basis, not only heart rate but also diastolic and systolic intervals, systolic and diastolic diameters, percent fractional shortening, contraction wave velocity, and cardiac arrhythmicity. Here, we present a detailed analysis of hearts from adult Drosophila, 2-3-day-old zebrafish larva, and 8-day-old mouse embryos, indicating that our methodology is potentially applicable to an array of biological models. We detect progressive age-related changes in fly hearts as well as subtle but distinct cardiac deficits in Tbx5 heterozygote mutant zebrafish. Our methodology for quantifying cardiac function in these genetically tractable model systems should provide valuable insights into the genetics of heart function.

[1]  B. Bruneau,et al.  Tbx5-dependent pathway regulating diastolic function in congenital heart disease , 2008, Proceedings of the National Academy of Sciences.

[2]  B. Bruneau The developmental genetics of congenital heart disease , 2008, Nature.

[3]  Karen Ocorr,et al.  Myosin transducer mutations differentially affect motor function, myofibril structure, and the performance of skeletal and cardiac muscles. , 2007, Molecular biology of the cell.

[4]  L. T. Wasserthal Drosophila flies combine periodic heartbeat reversal with a circulation in the anterior body mediated by a newly discovered anterior pair of ostial valves and `venous' channels , 2007, Journal of Experimental Biology.

[5]  Li Qian,et al.  Genetic control of heart function and aging in Drosophila. , 2007, Trends in cardiovascular medicine.

[6]  David Gerson,et al.  Two‐Dimensional Assessment of Right Ventricular Function: An Echocardiographic–MRI Correlative Study , 2007, Echocardiography.

[7]  Karen Ocorr,et al.  KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging , 2007, Proceedings of the National Academy of Sciences.

[8]  Michael Liebling,et al.  Rapid three‐dimensional imaging and analysis of the beating embryonic heart reveals functional changes during development , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[9]  Karen Ocorr,et al.  The ATP-sensitive potassium (KATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman , 2006, Proceedings of the National Academy of Sciences.

[10]  P. Wolf,et al.  Heart disease and stroke statistics--2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2006, Circulation.

[11]  Joseph A Izatt,et al.  Drosophila as a model for the identification of genes causing adult human heart disease , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Robin L. Cooper,et al.  Direct influence of serotonin on the larval heart of Drosophila melanogaster , 2006, Journal of Comparative Physiology B.

[13]  M. Ramaswami,et al.  Conditional mutations in SERCA, the Sarco-endoplasmic reticulum Ca2+-ATPase, alter heart rate and rhythmicity in Drosophila , 2006, Journal of Comparative Physiology B.

[14]  Wolfgang Rottbauer,et al.  High-throughput assay for small molecules that modulate zebrafish embryonic heart rate , 2005, Nature chemical biology.

[15]  R. Levine,et al.  Glutamatergic Innervation of the Heart Initiates Retrograde Contractions in Adult Drosophila melanogaster , 2005, The Journal of Neuroscience.

[16]  H. Dowse,et al.  MUTATIONS IN AND DELETIONS OF THE Ca2+ CHANNEL-ENCODING GENE CACOPHONY, WHICH AFFECT COURTSHIP SONG IN DROSOPHILA, HAVE NOVEL EFFECTS ON HEARTBEATING , 2005, Journal of neurogenetics.

[17]  R. Bodmer,et al.  2.6 – Heart Development and Function , 2005 .

[18]  R. Bodmer,et al.  Insulin regulation of heart function in aging fruit flies , 2004, Nature Genetics.

[19]  G. Gibson,et al.  Effects of Population Structure and Sex on Association Between Serotonin Receptors and Drosophila Heart Rate , 2004, Genetics.

[20]  T. Sacchi,et al.  History of the evolution of echocardiography. , 2004, International journal of cardiology.

[21]  Rolf Bodmer,et al.  Screening assays for heart function mutants in Drosophila. , 2004, BioTechniques.

[22]  D. Roden Human genomics and its impact on arrhythmias. , 2004, Trends in cardiovascular medicine.

[23]  John S. Strobel,et al.  Nonpharmacologic Validation of the Intrinsic Heart Rate in Cardiac Transplant Recipients , 1999, Journal of Interventional Cardiac Electrophysiology.

[24]  H. Dowse,et al.  Effects of deuterium oxide and temperature on heart rate in Drosophila melanogaster , 2004, Journal of Comparative Physiology B.

[25]  Claudia E Korcarz,et al.  Use of echocardiography for the phenotypic assessment of genetically altered mice. , 2003, Physiological genomics.

[26]  D. Turnbull,et al.  Onset of Cardiac Function During Early Mouse Embryogenesis Coincides With Entry of Primitive Erythroblasts Into the Embryo Proper , 2003, Circulation research.

[27]  A. Wong,et al.  Two-Photon Calcium Imaging Reveals an Odor-Evoked Map of Activity in the Fly Brain , 2003, Cell.

[28]  M. Fishman,et al.  The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome. , 2002, Development.

[29]  H. Dowse,et al.  Modulation of the cardiac pacemaker of Drosophila: cellular mechanisms , 2002, Journal of Comparative Physiology B.

[30]  J. Schmitt,et al.  A Murine Model of Holt-Oram Syndrome Defines Roles of the T-Box Transcription Factor Tbx5 in Cardiogenesis and Disease , 2001, Cell.

[31]  S. Rivkees,et al.  Ontogeny of humoral heart rate regulation in the embryonic mouse. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[32]  G. Theophilidis,et al.  An in vitro method for recording the electrical activity of the isolated heart of the adult Drosophila melanogaster , 2001, In Vitro Cellular & Developmental Biology - Animal.

[33]  A. McCulloch,et al.  Age-Associated Cardiac Dysfunction in Drosophila melanogaster , 2001, Circulation research.

[34]  G. Gibson,et al.  Quantitative trait loci for the monoamine-related traits heart rate and headless behavior in Drosophila melanogaster. , 2001, Genetics.

[35]  T. Opthof,et al.  The normal range and determinants of the intrinsic heart rate in man. , 2000, Cardiovascular research.

[36]  G. Gibson,et al.  Genetic variation affecting heart rate in Drosophila melanogaster. , 1999, Genetical research.

[37]  K. Paisley,et al.  Neural transmitters and a peptide modulate Drosophila heart rate , 1999, Peptides.

[38]  H. Dowse,et al.  Modulation of Drosophila heartbeat by neurotransmitters , 1997, Journal of Comparative Physiology B.

[39]  S. Singh,et al.  Pharmacological analysis of heartbeat in Drosophila. , 1995, Journal of neurobiology.

[40]  H. Dowse,et al.  A congenital heart defect in Drosophila caused by an action-potential mutation. , 1995, Journal of neurogenetics.

[41]  J. Gardin,et al.  Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). , 1994, The American journal of cardiology.

[42]  R. I. Woodruff,et al.  The osmolarity of adult Drosophila hemolymph and its effect on oocyte-nurse cell electrical polarity. , 1994, Developmental biology.

[43]  M. Fishman,et al.  Cardiovascular development in the zebrafish. I. Myocardial fate map and heart tube formation. , 1993, Development.