On the Morphology of the Drosophila Heart

Rotstein, Bárbara; Paululat, Achim

doi:10.3390/jcdd3020015

Cited by 74 publications

(78 citation statements)

References 83 publications

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“…The Drosophila heart is a muscular tube of cardiomyocytes that runs along the dorsal midline of the animal. It is responsible for pumping hemolymph, a plasma-like fluid, throughout the body in an open circulatory system (Rotstein and Paululat, 2016). Importantly, the contractile physiology of the Drosophila heart, including cardiomyocyte Ca 2+ transport mechanisms and sarcomere composition, is highly conserved with mammals (Lin et al, 2011;Ocorr et al, 2007), and the genetic and functional bases of many cardiomyopathies can be readily modeled and analyzed in flies (Piazza and Wessells, 2011 disorganized and loosely spaced in Stim and Orai suppressed hearts, further consistent with disrupted contractile physiology.…”

Section: Introductionmentioning

confidence: 82%

Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart

Petersen

Wolf

Smyth

2019

Preprint

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Store-operated Ca 2+ entry (SOCE) is an essential Ca 2+ signaling and homeostatic mechanism present in nearly all animal cells. SOCE refers to influx of Ca 2+ into cells that is activated by depletion of endoplasmic or sarcoplasmic reticulum stores (ER/SR) Ca 2+ stores. In the SOCE pathway, STIM proteins function as Ca 2+ sensors in the ER, and upon ER Ca 2+ store depletion STIM rearranges to ER-plasma membrane junctions where it activates Orai Ca 2+ influx channels. Multiple studies have implicated STIM and Orai mediated SOCE in the pathogenesis of cardiac hypertrophy. Importantly however, the functional roles of SOCE in normal heart physiology have not been well defined. We have addressed this in Drosophila melanogaster, a powerful animal model of cardiac development and physiology. We show that heart specific suppression of Drosophila Stim and Orai resulted in reduced contractility consistent with dilated cardiomyopathy, characterized by increased end diastolic and end systolic dimensions and decreased fractional shortening. Reduced contractility was apparent in larval hearts and became more pronounced in adults. Myofibers were disorganized and more widely spaced in larval and adult hearts with Stim and Orai RNAi as compared to controls, possibly reflecting decompensation or upregulated stress response signaling due to altered Ca 2+ homeostasis.Lastly, we show that reduced heart function significantly affected animal health and viability, as animals with heart specific Stim and Orai suppression exhibited significant delays in postembryonic development and adults died significantly earlier than controls. Collectively, our results demonstrate that SOCE is essential for normal heart physiology and establishDrosophila as an important model for delineation of functional SOCE roles in cardiomyocytes.

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Section: Introductionmentioning

confidence: 82%

Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart

Petersen

Wolf

Smyth

2019

Preprint

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“…In the larva, one pair of cardiomyocytes, which is the 34th pair of cells counted from the anterior, builds the intracardiac valve that partitions the heart tube into an anterior aorta and a posterior heart chamber (Lehmacher et al, 2012;Medioni et al, 2009;Rotstein and Paululat, 2016). During metamorphosis, two additional valves differentiate, resulting in three intracardiac valves in total that subdivide the adult heart into four chambers.…”

Section: Resultsmentioning

confidence: 99%

“…During metamorphosis, two additional valves differentiate, resulting in three intracardiac valves in total that subdivide the adult heart into four chambers. The valves in the adult fly are formed by the 22nd, the 28th and the 34th pair of cardiomyocytes (Lehmacher et al, 2012;Rotstein and Paululat, 2016;Tang et al, 2014;Zeitouni et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

Formation and function of intracardiac valve cells in the Drosophila heart

Lammers

Abeln

Hüsken

et al. 2017

Journal of Experimental Biology

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Drosophila harbours a simple tubular heart that ensures haemolymph circulation within the body. The heart is built by a few different cell types, including cardiomyocytes that define the luminal heart channel and ostia cells that constitute openings in the heart wall allowing haemolymph to enter the heart chamber. Regulation of flow directionality within a tube, such as blood flow in arteries or insect haemolymph within the heart lumen, requires a dedicated gate, valve or flap-like structure that prevents backflow of fluids. In the Drosophila heart, intracardiac valves provide this directionality of haemolymph streaming, with one valve being present in larvae and three valves in the adult fly. Each valve is built by two specialised cardiomyocytes that exhibit a unique histology. We found that the capacity to open and close the heart lumen relies on a unique myofibrillar setting as well as on the presence of large membranous vesicles. These vesicles are of endocytic origin and probably represent unique organelles of valve cells. Moreover, we characterised the working mode of the cells in real time. Valve cells exhibit a highly flexible shape and, during each heartbeat, oscillating shape changes result in closing and opening of the heart channel. Finally, we identified a set of novel valve cell markers useful for future in-depth analyses of cell differentiation in wild-type and mutant animals.

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“…To determine the cardiac function of Stj, we first tested whether this protein indeed accumulates in the adult fly heart. A weak cytoplasmic Stj signal associated with circular myofibers of cardiomyocytes and a strong signal in the myofibers of ventral longitudinal muscle (VLM) underlying the heart tube (Rotstein and Paululat, 2016) was visible in the adult Drosophila heart (Figure 5A and scheme Figure 5B) stained with anti-Stj antibody (Neely et al, 2010). This suggested that low stj levels in cardiac cells could have functional significance.…”

Section: Increased Cardiac Expression Of Stj Involves 3'utr Regulatiomentioning

confidence: 94%

Straightjacket/α2δ3deregulation is associated with cardiac conduction defects in Myotonic Dystrophy type 1

Plantie

Nakamori

Renaud

et al. 2018

Preprint

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Cardiac conduction defects decrease life expectancy in myotonic dystrophy type 1 (DM1), a complex toxic CTG repeat disorder involving misbalance between two RNAbinding factors, MBNL1 and CELF1. How this pathogenic DM1 condition translates into cardiac conduction disorders remains poorly understood. Here, we simulated MBNL1 and CELF1 misbalance in the Drosophila heart and identified associated gene deregulations using TU-tagging based transcriptional profiling of cardiac cells. We detected deregulations of several genes controlling cellular calcium levels and among them increased expression of straightjacket/α2δ3 that encodes a regulatory subunit of a voltage-gated calcium channel.Straightjacket overexpression in the fly heart leads to asynchronous heart beating, a hallmark of affected conduction, whereas cardiac straightjacket knockdown improves these symptoms in DM1 fly models. We also show that ventricular α2δ3 expression is low in healthy mice and humans but significantly elevated in ventricular muscles from DM1 patients with conduction defects. Taken together, this suggests that reducing the straightjacket/α2δ3 transcript levels in ventricular cardiomyocytes could represent a strategy to prevent conduction defects and in particular intraventricular conduction delay associated with DM1 pathology.

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On the Morphology of the Drosophila Heart

Cited by 74 publications

References 83 publications

Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart

Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart

Formation and function of intracardiac valve cells in the Drosophila heart

Straightjacket/α2δ3deregulation is associated with cardiac conduction defects in Myotonic Dystrophy type 1

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