heart of glass Regulates the Concentric Growth of the Heart in Zebrafish

Mably, John D.; Burns, C. Geoffrey; Chen, Jau-Nian; Fishman, Mark C.; Mohideen, Manzoor-Ali P.K.

doi:10.1016/j.cub.2003.11.055

Cited by 229 publications

(235 citation statements)

References 46 publications

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“…To test the idea that progenitor cell populations give rise to new CMs during homeostasis, we assessed CM maturation in the cmlc2:nRFP transgenic line, a strain that reports a slow-folding, nuclear-localized DsRed2 protein under control of the cardiac myosin light chain 2 (myl7 -Zebrafish Information Network) promoter (Mably et al, 2003). Mature CMs in these transgenic fish show nuclear-localized DsRed fluorescence.…”

Section: Developmentmentioning

confidence: 99%

Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish

et al. 2008

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The heart maintains structural and functional integrity during years of continual contraction, but the extent to which new cell creation participates in cardiac homeostasis is unclear. Here, we assessed cellular and molecular mechanisms of cardiac homeostasis in zebrafish, which display indeterminate growth and possess an unusual capacity to regenerate after acute cardiac injury. Lowering fish density in the aquarium triggered rapid animal growth and robust cardiomyocyte proliferation throughout the adult ventricle, greater than that observed during slow animal growth or size maintenance. Rapid animal growth also induced strong expression of the embryonic epicardial markers raldh2 (aldh1a2) and tbx18 in adult epicardial tissue. Pulse-chase dye labeling experiments revealed that the epicardium recurrently contributes cells to the ventricular wall, indicating an active homeostatic process. Inhibition of signaling by Fibroblast growth factors (Fgfs) decreased this epicardial supplementation of the ventricular wall in growing zebrafish, and led to spontaneous ventricular scarring in animals maintaining cardiac size. Our results demonstrate that the adult zebrafish ventricle grows and is maintained by cardiomyocyte hyperplasia, and that epicardial cells are added to the ventricle in an Fgf-dependent fashion to support homeostasis.

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Section: Developmentmentioning

confidence: 99%

Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish

et al. 2008

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“…Mutations in the heart of glass (heg), santa (krit1), and valentine (ccm2) genes do not seem to influence the shape of the heart tube, but they do cause severe distortion of chamber shape: the mutant hearts have thin-walled, extremely dilated chambers [35,36]. All three of these genes are expressed in endothelial cells, with heg clearly being expressed in the endocardium, suggesting that endocardial-myocardial signaling plays a key role in regulating chamber wall thickening.…”

Section: Defining Cardiac Cytoarchitecture: Subcellular Mechanics Of mentioning

confidence: 99%

Illuminating cardiac development: Advances in imaging add new dimensions to the utility of zebrafish genetics

Schoenebeck

Yelon

2007

Seminars in Cell & Developmental Biology

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The use of the zebrafish as a model organism for the analysis of cardiac development is no longer proof-of-principle science. Over the last decade, the identification of a variety of zebrafish mutations and the subsequent cloning of mutated genes have revealed many critical regulators of cardiogenesis. More recently, increasingly sophisticated techniques for phenotypic characterization have facilitated analysis of the specific mechanisms by which key genes drive cardiac specification, morphogenesis, and function. Future enrichment of the arsenal of experimental strategies available for zebrafish should continue the yield of high returns from such a small source.

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“…For the heart, part of such morphogenesis reflects control of overall cell number (Rottbauer et al, 2001;Rottbauer et al, 2002). Others control development of cells along two axes: anterior-posterior (Stainier and Fishman, 1992) and concentric (Mably et al, 2003). During the first stage of primitive heart tube formation the heart grows in essentially an anteriorposterior direction, with each of the two chambers constituted by a single-layered myocardium around the single layer of endocardium.…”

Section: Introductionmentioning

confidence: 99%

santaandvalentinepattern concentric growth of cardiac myocardium in the zebrafish

et al. 2006

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During embryogenesis, the myocardial layer of the primitive heart tube grows outward from the endocardial-lined lumen, with new cells added to generate concentric thickness to the wall. This is a key evolutionary step,demarcating vertebrates from more primitive chordates, and is essential for normal cardiac function. Zebrafish embryos with the recessive lethal mutations santa (san) and valentine (vtn) do not thicken, but do add the proper number of cells to the myocardium. Consequently, the heart chambers are huge, constituted of a monolayered myocardium lined by endocardium. This phenotype is similar to that of the heart of glass (heg) mutation, which we described previously as a novel endocardial expressed gene. By positional cloning, we here identify san as the zebrafish homolog of human CCM1, and vtn as the homolog of human CCM2. Dominant mutations of either in humans cause vascular anomalies in the brain, known as cerebral cavernous malformations. The synergistic effects of morpholino pairs indicate that san, vtn and heg are in a genetic pathway, and san and vtncontain protein motifs, NPxY and PTB domain, respectively, known to interact. This suggests that concentric growth of the myocardium, crucial for blood pressure generation, is dictated by a heg-san-vtnsignaling pathway.

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heart of glass Regulates the Concentric Growth of the Heart in Zebrafish

Cited by 229 publications

References 46 publications

Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish

Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish

Illuminating cardiac development: Advances in imaging add new dimensions to the utility of zebrafish genetics

santaandvalentinepattern concentric growth of cardiac myocardium in the zebrafish

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