Presence of Functional Sarcoplasmic Reticulum in the Developing Heart and Its Confinement to Chamber Myocardium

Moorman, Antoon F.M.; Schumacher, Cees A.; Boer, P A de; Hagoort, Jaco; Bezstarosti, Karel; Hoff, Maurice J.B. van den; Wagenaar, Gerry T. M.; Lamers, Jos M. J.; Wuytack, Frank; Christoffels, Vincent M.; Fiolet, J.W.T.

doi:10.1006/dbio.2000.9752

Cited by 84 publications

(58 citation statements)

References 49 publications

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“…Cardiac precursors proliferate and migrate to the embryonic midline to form a linear heart tube that is segmentally patterned along its anteroposterior axis into regions ultimately giving rise to the atrial and ventricular chambers. Rightward looping of the linear heart tube followed by balloon-like growth of the outer curvatures of the ventricular segments generates the right and left ventricular chambers Moorman et al, 2000). Notably, each cardiac chamber possesses distinct physiological functions and patterns of gene expression.…”

Section: Introductionmentioning

confidence: 99%

The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner

et al. 2005

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The basic helix-loop-helix transcription factors Hand1 and Hand2 display dynamic and spatially restricted expression patterns in the developing heart. Mice that lack Hand2 die at embryonic day 10.5 from right ventricular hypoplasia and vascular defects, whereas mice that lack Hand1 die at embryonic day 8.5 from placental and extra-embryonic abnormalities that preclude analysis of its potential role in later stages of heart development. To determine the cardiac functions of Hand1, we generated mice harboring a conditional Hand1-null allele and excised the gene by cardiac-specific expression of Cre recombinase. Embryos homozygous for the cardiac Hand1 gene deletion displayed defects in the left ventricle and endocardial cushions, and exhibited dysregulated ventricular gene expression. However, these embryos survived until the perinatal period when they died from a spectrum of cardiac abnormalities. Creation of Hand1/2 double mutant mice revealed gene dose-sensitive functions of Hand transcription factors in the control of cardiac morphogenesis and ventricular gene expression. These findings demonstrate that Hand factors play pivotal and partially redundant roles in cardiac morphogenesis, cardiomyocyte differentiation and cardiac-specific transcription.

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Section: Introductionmentioning

confidence: 99%

The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner

et al. 2005

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“…Soon thereafter, these cells converge along the midline of the embryo to form a linear heart tube that initiates peristaltic contractions. Generation of the mature multi-chambered heart from the linear heart tube involves a complex series of events that include rightward looping and diversification of cardiac cell types, balloon-like growth and septation to form the cardiac chambers, and connection to the inflow and outflow tract vasculature Moorman et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart

et al. 2005

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The vertebrate heart is assembled during embryogenesis in a modular manner from different populations of precursor cells. The right ventricular chamber and outflow tract are derived primarily from a population of progenitors known as the anterior heart field. These regions of the heart are severely hypoplastic in mutant mice lacking the myocyte enhancer factor 2C (MEF2C) and BOP transcription factors, suggesting that these cardiogenic regulatory factors may act in a common pathway for development of the anterior heart field and its derivatives. We show that Bop expression in the developing heart depends on the direct binding of MEF2C to a MEF2-response element in the Bop promoter that is necessary and sufficient to recapitulate endogenous Bop expression in the anterior heart field and its cardiac derivatives during mouse development. The Boppromoter also directs transcription in the skeletal muscle lineage, but only cardiac expression is dependent on MEF2. These findings identify Bopas an essential downstream effector gene of MEF2C in the developing heart, and reveal a transcriptional cascade involved in development of the anterior heart field and its derivatives.

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“…In primary heart tubes of developing chicken embryos and the outflow tract of early rat embryonic heart, a functional SR is lacking (3), and in mice, regulated calcium release via the RyR in early embryonic hearts is thought to be of little importance (4). The presumption is that sarcolemmal Ca 2ϩ currents working with the Na ϩ ͞Ca 2ϩ exchanger play a predominant role in the regulation of cytosolic Ca 2ϩ to drive the heart's contraction during early cardiac development, and that RyR2 is required primarily to participate in the maintenance of intracellular Ca 2ϩ homeostasis.…”

mentioning

confidence: 99%

The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development

Huang

Tweedie

Wang

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

108

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In adult myocardium, the heartbeat originates from the sequential activation of ionic currents in pacemaker cells of the sinoatrial node. Ca 2؉ release via the ryanodine receptor (RyR) modulates the rate at which these cells beat. In contrast, the mechanisms that regulate heart rate during early cardiac development are poorly understood. Embryonic stem (ES) cells can differentiate into spontaneously contracting myocytes whose beating rate increases with differentiation time. These cells thus offer an opportunity to determine the mechanisms that regulate heart rate during development. Here we show that the increase in heart rate with differentiation is markedly depressed in ES cell-derived cardiomyocytes with a functional knockout (KO) of the cardiac ryanodine receptor (RyR2). KO myocytes show a slowing of the rate of spontaneous diastolic depolarization and an absence of calcium sparks. The depressed rate of pacemaker potential can be mimicked in wild-type myocytes by ryanodine, and rescued in KO myocytes with herpes simplex virus (HSV)-1 amplicons containing full-length RyR2. We conclude that a functional RyR2 is crucial to the progressive increase in heart rate during differentiation of ES cell-derived cardiomyocytes, consistent with a mechanism that couples Ca 2؉ release via RyR before an action potential with activation of an inward current that accelerates membrane depolarization.

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Presence of Functional Sarcoplasmic Reticulum in the Developing Heart and Its Confinement to Chamber Myocardium

Cited by 84 publications

References 49 publications

The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner

The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner

BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart

The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development

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